Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
hui lu
 -- 3297 2023-02-24 04:24:49 |
2 format
Jason Zhu
 Meta information modification 3297 2023-02-27 06:34:41 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Dong, Y.; Zhou, H.; Alhaskawi, A.; Wang, Z.; Lai, J.; Yao, C.; Liu, Z.; Ezzi, S.H.A.; Goutham Kota, V.; Hasan Abdulla Hasan Abdulla, M.; et al. Application of FAPI PET/CT in Cancers. Encyclopedia. Available online: https://encyclopedia.pub/entry/41609 (accessed on 22 December 2024).
Dong Y, Zhou H, Alhaskawi A, Wang Z, Lai J, Yao C, et al. Application of FAPI PET/CT in Cancers. Encyclopedia. Available at: https://encyclopedia.pub/entry/41609. Accessed December 22, 2024.
Dong, Yanzhao, Hai-Ying Zhou, Ahmad Alhaskawi, Zewei Wang, Jingtian Lai, Chengjun Yao, Zhenfeng Liu, Sohaib Hasan Abdullah Ezzi, Vishnu Goutham Kota, Mohamed Hasan Abdulla Hasan Abdulla, et al. "Application of FAPI PET/CT in Cancers" Encyclopedia, https://encyclopedia.pub/entry/41609 (accessed December 22, 2024).
Dong, Y., Zhou, H., Alhaskawi, A., Wang, Z., Lai, J., Yao, C., Liu, Z., Ezzi, S.H.A., Goutham Kota, V., Hasan Abdulla Hasan Abdulla, M., & Lu, H. (2023, February 24). Application of FAPI PET/CT in Cancers. In Encyclopedia. https://encyclopedia.pub/entry/41609
Dong, Yanzhao, et al. "Application of FAPI PET/CT in Cancers." Encyclopedia. Web. 24 February, 2023.
Application of FAPI PET/CT in Cancers
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cancers15041193

Cancer represents a major cause of death worldwide and is characterized by the uncontrolled proliferation of abnormal cells that escape immune regulation. It is now understood that cancer-associated fibroblasts (CAFs), which express specific fibroblast activation protein (FAP), are critical participants in tumor development and metastasis. Researchers have developed various FAP-targeted probes for imaging of different tumors from antibodies to boronic acid-based inhibitor molecules and determined that quinoline-based FAP inhibitors (FAPIs) are the most appropriate candidate as the radiopharmaceutical for FAPI PET/CT imaging. When applied clinically, FAPI PET/CT yielded satisfactory results.

FAPI PET/CT imaging cancers

1. Introduction

1.1. General Background, Gastric Cancer, and Peritoneal Cancer

Gastric cancer in humans can be histologically categorized as diffuse and intestinal-type carcinoma according to the Lauren classification [1]. Although both types express high levels of FAP, higher levels have been documented in the intestinal type. In gastric carcinoma, FAP is majorly confined within carcinoma cells, which is different from many other tumor types [2][3]. Studies have shown that elevated FAP expression is associated with higher tumor grades, increased incidence of lymph node and lymphatic spread, peritoneal invasion, poor prognosis, and worse overall survival [4][5]. Gastric cancer models and related research have observed increased levels of ex vivo proliferation and migration of gastric carcinoma cells and elevated in vivo resistance against anti-PD1 therapy in co-cultures with FAP-expressing fibroblasts, and increased tumor size in vivo [5][6]. Compared with the traditional 18F-FDG PET/CT, the sensitivity of 68Ga-FAPI-04 PET/CT is significantly higher in detecting primary gastric tumors, positive lymph node and lymphatic metastasis, and distant metastases, especially in signet-ring cell carcinomas and mucinous adenocarcinomas [7]. Studies have reported the superiority of FAPI over FDG as tracers for PET/CT by measuring the SUVmax during gastric cancer detection and diagnosis [8].

1.2. Colorectal Cancer

While FAP is ubiquitously expressed at a low to non-detectable level in normal tissue, high levels of FAP have been detected in human colorectal cancer cells and adjacent stroma, even at early stages [9][10]. Researchers have recently proposed that FAP plays a potential role in colorectal tumor migration or invasion since elevated levels of FAP have been detected in the tumor margin compared with the tumor center, and the pattern is reversed post-radiotherapy, indicating a role of FAP in tumor remodeling following radiological damage [11]. It has been established that an elevated level of FAP is associated with more advanced invasion depth, lymph node metastases, stage of the tumor, and, consequently, worse prognosis and overall survival [11][12]. On the other hand, FAP expression in tumors is associated with altered immunological traits, especially in the immune cell populations. For instance, elevated FAP is correlated with increased CD11b+ cell expression and decreased CD3+ cell expression [13]. Importantly, 68Ga-DOTA-FAPI-04 PET/CT showed similar sensitivities during the detection of primary colorectal tumors compared to FDG imaging while displaying higher SUVmax in the detection of lymph node metastases [14].

1.3. Hepatobiliary and Pancreatic Carcinoma

As one of the common clinical malignancies, hepatobiliary carcinomas affect over 900,000 people globally, posing a serious challenge for families and healthcare professionals [15]. A recent study by Zou et al. revealed that the expression of FAP was induced by hypoxia and correlated with poor clinical outcomes. Furthermore, it was determined that the expression levels of FAP and HIF-1α were closely correlated via immunohistochemistry analysis, Western blot and qRT-PCR analysis conducted on a 138-patient cohort [16]. Regarding hepatobiliary malignancies, FAPI-based imaging methods, especially 68Ga-FAPI-04 PET/CT, demonstrated better sensitivity and accuracy in detecting the primary tumor, lymph node metastases, and distant metastases in comparison to FDG-based imaging systems [17]. In the case of hepatocellular carcinomas and intrahepatic cholangiocarcinoma, FAPI-04 has demonstrated better performance in identifying primary liver tumors and extrahepatic metastases with higher tumor uptake and lower hepatic background uptake compared with 18F-FDG [18][19][20][21].
Positive FAP staining is observed in 90% of human pancreatic ductal adenocarcinomas (PDAC), while PDAC tumor cells and stromal cells were positively stained in cultured cell lines, with the stroma adjacent to the tumor tissue showing the highest levels of FAP [22]. Current evidence suggests that low FAP expression correlates with increased pancreatic fibrosis, and high FAP expression is generally associated with adverse events, including lymphatic metastases, tumor recurrence, and mortality [23][24]. Interestingly, it has been documented that FAP-positive pancreatic stellate cells underwent CXCL1-mediated Akt phosphorylation, subsequently enhancing tumor migration and invasion [6]. A study showed that in vivo FAP deficiency could delay tumor onset and prolong the lifespan of mice, and FAP depletion or deficiency increased tumor necrosis and impeded metastasis, especially at distant sites [24]. Other murine experiments using the KPC mice model of human PDAC have also observed increased FAP expression in the premalignant and malignant lesions [25]. Overall, these studies have demonstrated a positive correlation between elevated FAP levels and increased risk of poor prognosis [22][24]. While many believe that FAP is correlated with worsened clinical outcomes, clinicians are endeavoring to leverage these characteristics of FAP in anti-tumor therapeutic regimens. For instance, FAP blockade in combination with radiotherapy against pancreatic adenocarcinoma in a murine model has shown satisfactory outcomes, which led to the conclusion that anti-tumor T cell infiltration and function in pancreatic adenocarcinoma is enhanced via this regimen [26]. However, the tumor clearance rate by the mentioned method was insufficient to improve prognosis or extend survival. These results call for more research into FAP/FAPI and its role in PDAC, and pancreatic cancer in general [23].

2. Brain Cancer

Although FAPI PET/CT has been extensively implemented in brain cancer research, the staging and subsequent treatment of brain cancers remain a significant conundrum, especially the determination of the tumor margins and invasion status. Glioma is the most common primary intracranial tumor with many subtypes. According to the World Health Organization, glioma can be categorized into isocitrate dehydrogenase (IDH) wild type and IDH mutant glioma types. The former type has been used to investigate the target affinity and specificity of FAPI-02 and FAPI-04 in animal studies, where 68GaFAPI-02/04 was used based on PET images. FAPI PET imaging showed a decreased tracer uptake in diffuse astrocytomas. On the other hand, increased tracer uptake by IDH-wildtype glioblastomas and high-grade IDH mutant astrocytomas was observed. PET images showed that FAPI-02 exhibits lower tumor accumulation and earlier elimination than FAPI-04 [27].
Lumbosacral myxopapillary ependymoma is a rare type of tumor that predominantly involves the conus medullaris, filum terminale, or cauda equina in the central nervous system. A recent study by Chongjia Li et al. revealed the diagnostic value of 68Ga-FAPI-04 PET/CT imaging in the current clinical settings [28]. 18F-FDG and 11C-MET showed a characteristic accumulation in high-grade ependymoma but brought little benefit in differentiating low-grade ependymoma from the background or non-neoplastic lesions. On the other hand, using 68Ga-FAPI-04 PET/CT imaging, low background uptake in FAPI was observed in the brain and spinal cord, which is suitable for the imaging of low-grade ependymoma. Other studies substantiated the diagnostic and management value of FAPI PET/CT imaging in primary benign intraosseous meningioma and schwannomas [29][30].

3. Neck and Ear, Nose, and Throat (ENT) Cancer

Head and neck cancers (HNCs) are among the most common malignancies worldwide, with more than half a million cases and a quarter million deaths reported annually. As an important part of traditional HNCs management, radiation therapy (RT) can significantly improve the overall prognosis and survival of patients. Despite its advantages, the shortcomings of RT include tumor recurrence, especially at the tumor margins, and toxicity to normal surrounding tissues [31][32]. The invasive and diffuse nature of HNCs and their tendency to infiltrate the surrounding tissue make diagnosis and treatment extremely challenging since conventional CT and MRI imaging exhibit poor ability to provide high-resolution images to contrast the tumor and surrounding tissues [32][33][34][35]. FDG PET/CT has been extensively applied for HNCs staging and treatment since its early application in 2015 by Schwartz D. et al. [36]. However, the application of FDG PET/CT is limited because of the high uptake rate of FDG by normal surrounding tissues, including muscles, the brain, salivary glands, and lymph nodes, which could result in a blurry background and the inability to differentiate tumors from inflamed or post-operative tissue [32]. Importantly, FAPI expression in HNCs is rarely influenced by the metabolic activity of the surrounding tissues, overcoming the limitations of FDG imaging.
The application of FAPI PET/CT in detecting HNCs has become a research hotspot in recent years. It has been shown that FAPI PET/CT could facilitate precision radiotherapy [37][38][39][40]. Indeed, it is widely acknowledged that FAPI PET/CT targets the HNCs more accurately and sensitizes the whole tumor to RT and chemoimmunotherapy via targeting CAF-specific cell surface markers, CAF-specific paracrine signaling pathways, and CAF-derived ECM. Given that FAP expression is exclusively high in primary lesions and metastases, harm and toxicity to the surrounding tissues are limited [41][42]. Manuel et al. measured the 68Ga-FAPI PET/CT uptake by adenoid cystic carcinoma (ACC) and determined that 68Ga-FAPI PET/CT identifies more metastatic lesions compared with CT or MRI, which helps in upstaging the ACC and improving the RT by increasing the accuracy of the target gross tumor volume (GTV) delineation confirmed by SUVmax and TBR [43]. In a pilot study on the delineation of HNCs for RT planning, M. Syed et al. investigated an existing database of 14 HNC patients using both CE-CT for conventional GTVs and 68Ga FAPI PET/CT for FAPI-GTVs, which was later analyzed with syngo. via software. An improved quality of imaging was obtained, and it was concluded that a greater initial dosage was required for RT planning due to the enhanced detection ability of lymph node metastases and distant metastases [44]. Chunxia et al. compared the value of 68Ga-FAPI PET/MR and 18F-FDG PET/MR in diagnosing and staging of nasopharyngeal carcinoma (NPC) patients and observed that 68Ga-FAPI PET/MR was superior in evaluating intracranial invasion, skull base, and the small metastases [45]. However, FAPI PET/CT still warrants further improvement. In this respect, a recent case report revealed that FAPI PET/CT yielded repeated false positive results in a patient suffering from esophagitis, possibly due to its inability to differentiate between cancerous tissue and inflammation [46].
On the other hand, in 2022, it was reported that FAPI-guided targeted therapy yielded a substantial effect in a patient suffering from aggressive medullary thyroid carcinoma. Importantly, this was the first-in-human attempt of 68Ga-DOTA.SA.FAPI–guided 177Lu-DOTAGA, a novel combination of radiopharmaceuticals with FAPI imaging modalities [47]. This success corroborates that FAPI imaging can be harnessed to guide the treatment of aggressive medullary thyroid cancer and other HNCs.

4.. Lung Cancer

18F-FDG PET/CT is now recommended by the National Comprehensive Cancer Network Guidelines, along with contrast-enhanced brain MRI, as the standard evaluation method for clinically staging lung cancer pre- and post-treatment [48][49]. However, concerns have been raised regarding its compromised ability to detect bone and pleural metastases of lung cancer [50][51]. To resolve this issue, Kratochwil C. et al. and Loktev A. et al. subsequently introduced 68Ga-FAPI PET/CT to compensate for these defects caused by the imaging principle of FDG, which is metabolic imaging [52][53]. Current evidence suggests that 68Ga-FAPI PET/CT is superior to 18F-FDG PET/CT in diagnosing and staging lung cancer, and it has already been applied clinically for detecting early-stage lung cancer. However, it should be noted that 68Ga-FAPI PET/CT is not a routine examination for diagnosing the primary lesions or metastases of patients with lung cancers [54]. Furthermore, some studies compared the two imaging modalities regarding primary lung cancers and suspected liver or adrenal gland metastases from lung cancer. It was determined that 68Ga-FAPI PET/CT detects more metastatic lesions in the liver, lungs, pleura, bone, and brain, and the SUVmax and TBR values were higher in bone and hepatic lesions with 68Ga-FAPI PET/CT [55]. Furthermore, Giesel L. et al. and Kratochwil C. et al. demonstrated that 68Ga-FAPI PET/CT could more easily detect mediastinal lymph node metastasis with higher uptake and TBR [37][53].
In contrast with FDG PET/CT, 68Ga-FAPI PET/CT has low background radioactivity in the brain given that normal brain tissue only expresses low to non-detectable FAP levels while the metabolic rate is high, resulting in high background 18F-FDG uptake and adding to the difficulty in differentiating tumor from normal tissue. Therefore, FAPI imaging is more sensitive in detecting brain and leptomeningeal metastases from lung adenocarcinoma (ADC) [56].
It has been established that FAPI PET/CT could differentiate between various types of lung cancer (squamous cell carcinoma SCC, ADC, non-small cell lung cancer NSCLC, and small cell lung cancer) as primary tumors or metastatic lesions in different sites [57]. A retrospective study was conducted to estimate and compare the diagnostic accuracy between 18F-FDG and 68Ga-FAPI-04 PET/CT in NSCLC patients, which showed a better diagnostic accuracy of 68Ga-FAPI-04 PET/CT based on TNM staging, while there is no significant difference in SUV max, TBR values for the primary tumor [55][57][58][59]. Contrasting 68Ga-FAPI PET/CT studies have reported higher primary tumor SUV max than 18F-FDG, which may be attributed to the heterogeneity in clinical settings and more advanced tumor staging [60].
Another advantage of FAPI imaging is that 12 min post-injection of 68Ga-FAPI could achieve a higher SUV, providing a better-quality evaluation image of lung cancer at an earlier time, which limits the risk of deleterious side effects induced by prolonged circulating radiopharmaceuticals often observed with 18F-FDG [61]. In addition, the probability of false-negative results by 18F-FDG has been reported to be higher when no 18F-FDG uptake was detected in the lymph node of less than 10 mm in size or of small volume and low metabolic activity tumors, while 68Ga-FAPI PET/CT yielded correct diagnoses under such conditions [62][63][64].
However, benign pulmonary diseases may produce false-positive results during 18F-FDG PET/CT, such as tuberculosis, silicosis, and sarcoidosis [62][65][66]. For instance, Canan C. et al. reported false-positive results by 18F-FDG due to anthracosis in a 29-patient cohort of patients suffering from NSCLC, ADC, and SCC, where 18F-FDG and 68Ga-FAPI yielded 89.6% and 100% diagnostic accuracy, respectively [55]. While FAPI imaging is superior to FDG in diagnostic accuracy, it warrants further improvement, especially for differentiating between cancer and other pathological conditions including infection, inflammation, and fibrosis [67].

5. Breast Cancer

Targeting FAP has become a promising breast cancer imaging and treatment approach in recent years. In a cohort of 48 breast cancer patients, 68Ga-FAPI-04 PET/CT displayed superior diagnostic value in the number of detected lesions of primary tumors with higher SUVmax, lymphatic metastases, and distant metastases than 18F-FDG PET/CT [68]. Concerning the management of breast cancer, one of the earliest studies on FAP expression and relevance in breast cancer by Thomas Kelly et al. showed that FAP-α promotes tumor growth and invasion of breast cancer cells via non-enzymatic functions mediated by MMP-9 in a mouse model of human breast cancer [69].
Another early publication in this domain compared breast epithelial tumors with normal breast tissue and observed FAP overexpression in tumor stroma [70]. In 2011, Hua X. et al. proposed that the application of FAP staining resulted in the up-staging of ductal carcinoma in situ (DCIS) to DCIS with microenvironment invasion (DCIS-MI), which could facilitate fine-tuning of therapeutic management associated with DCIS and DCIS-MI [71].
Current evidence suggests that FAP expression in the stroma is higher in cases of invasive lobular carcinoma than in invasive carcinoma with no special characteristics or type [72]. In invasive ductal carcinoma, high-grade tumors and stroma with inflammation and adipocytes had higher FAP levels than those with desmoplastic, sclerotic, or normal-like stroma [73]. In benign breast tumors such as phyllodes tumors, higher levels of FAP mRNA correlated with malignant transformation, suggesting that, in addition to its prognostic value in DCIS, FAP represents a potential biomarker signaling malignancy [74].

6. Bone Tumors

Regarding potential applications in the musculoskeletal system, 68Ga-FAPI-04 PET/CT is mainly used to diagnose bone metastases of malignant tumors originating elsewhere rather than primary bone malignant tumors. Bone metastasis is a common complication in patients suffering from advanced malignant tumors involving the breast, prostate, lung, thyroid, kidney, etc. [75][76]. Indeed, early detection and timely treatment of bone metastases can significantly improve the quality of life and overall prognosis by avoiding complications ranging from cancer-associated osteoporosis to pathological fracture [77]. There is an increasing consensus that compared with 18F-FDG PET/CT, FAPI PET/CT yields a higher detection rate of bone metastases with high sensitivity, high uptake values, and high TBR [67][78][79]. Chen et al. showed that 68Ga-FAPI-04 PET/CT is superior to 18F-FDG PET/CT in detecting bone metastasis with significantly increased uptake by metastatic lesions (n = 9, median SUV 9.3 vs. 2.6, p = 0.008) [80]. These conclusions were corroborated by a retrospective analysis conducted by Wu et al., where a cohort of 75 patients underwent 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT, and the sensitivity for bone and visceral metastases was 83.8% vs. 59.5% (p = 0.004) [67].
However, false-positive results in benign bone lesions 68Ga-FAPI PET/CT have been reported, as observed in a case of a 72-year-old patient suffering from myositis ossificans, a benign orthopedic disorder [81]. Zheng et al. reported that both 18F-FDG and 68Ga-FAPI imaging led to a false-negative diagnosis of bone metastasis in a breast cancer patient, which is also the first case of a false-negative result of bone metastasis by FAPI imaging [82]. Accordingly, it is premature to conclude that 68Ga-FAPI is superior to 18F-FDG in detecting bone metastases or lesions, emphasizing the importance of further research.

7. Soft Tissue Tumors

Current research on the applications of FAPI PET/CT in cancer confirmed that FAPI led to high SUV values in sarcomas and distinct contrast to the background due to low background uptake [53][83][84][85]. Regarding the evaluation of diagnostic accuracy, 68Ga-FAPI PET/CT yielded a high positive predictive value in patient-based analysis (n = 27, 100%) and lesion-based analysis (n = 33, 97%), as well as high sensitivity (n = 28, 96%; n = 34, 94%) [86]. In addition, FAPI imaging has huge prospects to guide therapy against sarcomas given that various FAPI uptake rates have been observed at different stages of sarcomas [87][88]. In this respect, a recent study by Koerber et al. on seven types of sarcomas in 15 patients showed high uptake in FAPI in high-grade sarcomas, including undifferentiated pleomorphic sarcoma (UPS) and low uptake in low-grade sarcomas, which could be applied in RT [85]. Although 18F-FDG PET/CT is highly effective in diagnosing primary lesions, especially in high-grade sarcomas, FAPI is considered to possess superior diagnostic value, as shown in studies conducted by Macpherson et al. (n = 493), Charest et al. (n = 212) [89][90][91]. Studies by Bingxin Gu et al. have shown that FAPI is superior to 18F-FDG PET/CT (n = 45) in identifying recurrent lesions of liposarcoma, malignant solitary fibrous tumors, and invasive ductal carcinomas in sensitivity (97.52% vs. 65.96%), specificity (60.71% vs. 21.43%), positive predictive value (96.15% vs. 89.42%), negative predictive value (70.88% vs. 5.88%), and accuracy (94.19% vs. 61.94%), while on the other hand, 18F-FDG showed better diagnostic efficacy than FAPI PET/CT in identifying UPS and rhabdomyosarcoma [92]. Both imaging modalities yielded similar results in monitoring the recurrence of bone malignancies [92].
Apart from sarcomas, research on FAPI in detecting other soft tissue tumors, including malignant melanoma, remains relatively scarce [93]. Kgomotso Mokoala et al. presented a case of advanced cutaneous malignant melanoma with multiple organ metastasis, where FAPI yielded higher SUV values than FDG in the liver, lung, and left femoral head metastases but not for lung metastases [94]. However, in the case of a 65-year-old patient with metastatic uveal malignant melanoma, the SUV for FAPI was lower than FDG in the metastatic liver lesion while higher in both knee joints [95]. This discrepancy may result from the limited sample volume, highlighting the need for further investigation.

8. Other Cancer

The significant heterogeneity of the cell/extracellular microenvironment is associated with the prognosis of patients with lymphoma [96]. Depending on different phenotypes, CAFs may exhibit pro-tumor or anti-tumor effects in the TME [97]. Hodgkin lymphoma (HL) is characterized by the proliferation of fibroblasts in the TME. Studies have confirmed that FAP immunostaining is more intense in neoplasms, and FAPI uptake is significantly increased in HL lesions. However, compared with HL, FAP immunostaining and FAPI uptake are weaker in NHL except for aggressive NHL, especially diffuse large B-cell lymphoma [98]. The high TBR in FAPI images resulted in high contrast ratios for lymphoma lesions, especially in the brain, liver, and oropharynx, which can be very helpful in diagnosing lymphoma in these organs [99][100].

References

  1. Laurén, P. The Two Histological Main Types of Gastric Carcinoma: Diffuse and so-called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification. Acta Pathol. Microbiol. Scand. 1965, 64, 31–49.
  2. Okada, K.; Chen, W.T.; Iwasa, S.; Jin, X.; Yamane, T.; Ooi, A.; Mitsumata, M. Seprase, a Membrane-Type Serine Protease, Has Different Expression Patterns in Intestinal- and Diffuse-Type Gastric Cancer. Oncology 2003, 65, 363–370.
  3. Mori, Y.; Kono, K.; Matsumoto, Y.; Fujii, H.; Yamane, T.; Mitsumata, M.; Chen, W.-T. The Expression of a Type II Transmembrane Serine Protease (Seprase) in Human Gastric Carcinoma. Oncology 2004, 67, 411–419.
  4. Hu, M.; Qian, C.; Hu, Z.; Fei, B.; Zhou, H. Biomarkers in Tumor Microenvironment? Upregulation of Fibroblast Activation Protein-α Correlates with Gastric Cancer Progression and Poor Prognosis. OMICS A J. Integr. Biol. 2017, 21, 38–44.
  5. Wen, X.; He, X.; Jiao, F.; Wang, C.; Sun, Y.; Ren, X.; Li, Q. Fibroblast Activation Protein-α-Positive Fibroblasts Promote Gastric Cancer Progression and Resistance to Immune Checkpoint Blockade. Oncol. Res. 2017, 25, 629–640.
  6. Wen, Z.; Liu, Q.; Wu, J.; Xu, B.; Wang, J.; Liang, L.; Guo, Y.; Peng, M.; Zhao, Y.; Liao, Q. Fibroblast activation protein α-positive pancreatic stellate cells promote the migration and invasion of pancreatic cancer by CXCL1-mediated Akt phosphorylation. Ann. Transl. Med. 2019, 7, 532.
  7. Buyyounouski, M.K.; Klump, W.J.; Konski, A.; Wu, H.; Adler, L.P. FDG PET Imaging of Signet-Ring Cell Adenocarcinoma of the Stomach. Clin. Nucl. Med. 2005, 30, 118–119.
  8. Chen, R.; Yang, X.; Ng, Y.L.; Yu, X.; Huo, Y.; Xiao, X.; Zhang, C.; Chen, Y.; Zheng, C.; Li, L.; et al. First total-body kinetic modeling and parametric imaging of dynamic 68Ga-FAPI-04 PET in pancreatic and gastric cancer. J. Nucl. Med. 2023, 64.
  9. Iwasa, S.; Jin, X.; Okada, K.; Mitsumata, M.; Ooi, A. Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer. Cancer Lett. 2003, 199, 91–98.
  10. Henry, L.R.; Lee, H.O.; Lee, J.S.; Klein-Szanto, A.; Watts, P.; Ross, E.A.; Chen, W.-T.; Cheng, J.D. Clinical Implications of Fibroblast Activation Protein in Patients with Colon Cancer. Clin. Cancer Res. 2007, 13, 1736–1741.
  11. Wikberg, M.L.; Edin, S.; Lundberg, I.V.; Van Guelpen, B.; Dahlin, A.M.; Rutegård, J.; Stenling, R.; Öberg, Å.; Palmqvist, R. High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumor Biol. 2013, 34, 1013–1020.
  12. Fitzgerald, A.A.; Weiner, L.M. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020, 39, 783–803.
  13. Yang, X.; Lin, Y.; Shi, Y.; Li, B.; Liu, W.; Yin, W.; Dang, Y.; Chu, Y.; Fan, J.; He, R. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3–CCL2 Signaling. Cancer Res. 2016, 76, 4124–4135.
  14. Kömek, H.; Can, C.; Kaplan, I.; Gündoğan, C.; Kepenek, F.; Karaoglan, H.; Demirkıran, A.; Ebinç, S.; Güzel, Y.; Gündeş, E. Comparison of Ga-DOTA-FAPI-04 PET/CT and FDG PET/CT in colorectal cancer. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 3898–3909.
  15. Rumgay, H.; Arnold, M.; Ferlay, J.; Lesi, O.; Cabasag, C.J.; Vignat, J.; Laversanne, M.; McGlynn, K.A.; Soerjomataram, I. Global burden of primary liver cancer in 2020 and predictions to 2040. J. Hepatol. 2022, 77, 1598–1606.
  16. Zou, B.; Liu, X.; Zhang, B.; Gong, Y.; Cai, C.; Li, P.; Chen, J.; Xing, S.; Chen, J.; Peng, S.; et al. The Expression of FAP in Hepatocellular Carcinoma Cells is Induced by Hypoxia and Correlates with Poor Clinical Outcomes. J. Cancer 2018, 9, 3278–3286.
  17. Zhang, J.; He, Q.; Jiang, S.; Li, M.; Xue, H.; Zhang, D.; Li, S.; Peng, H.; Liang, J.; Liu, Z.; et al. FAPI PET/CT in the evaluation of focal liver lesions with FDG non-avidity. Eur. J. Nucl. Med. Mol. Imaging 2022, 50, 937–950.
  18. Loktev, A.; Lindner, T.; Burger, E.-M.; Altmann, A.; Giesel, F.; Kratochwil, C.; Debus, J.; Marme, F.; Jäger, D.; Mier, W.; et al. Development of Fibroblast Activation Protein-Targeted Radiotracers with Improved Tumor Retention. J. Nucl. Med. 2019, 60, 1421–1429.
  19. Guo, W.; Pang, Y.; Yao, L.; Zhao, L.; Fan, C.; Ke, J.; Guo, P.; Hao, B.; Fu, H.; Xie, C.; et al. Imaging fibroblast activation protein in liver cancer: A single-center post hoc retrospective analysis to compare Ga-FAPI-04 PET/CT versus MRI and -FDG PET/CT. Eur. J. Nucl. Med. Mol. Imaging 2020, 48, 1604–1617.
  20. Zhao, L.; Chen, J.; Pang, Y.; Fu, K.; Shang, Q.; Wu, H.; Sun, L.; Lin, Q.; Chen, H. Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review. Theranostics 2022, 12, 1557–1569.
  21. Zhao, L.; Chen, J.; Pang, Y.; Fang, J.; Fu, K.; Meng, L.; Zhang, X.; Guo, Z.; Wu, H.; Sun, L.; et al. Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy. Mol. Pharm. 2022, 19, 3640–3651.
  22. Shi, M.; Yu, D.-H.; Chen, Y.; Zhao, C.-Y.; Zhang, J.; Liu, Q.-H.; Ni, C.-R.; Zhu, M.-H. Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J. Gastroenterol. 2012, 18, 840–846.
  23. Cohen, S.J.; Alpaugh, R.K.; Palazzo, I.; Meropol, N.J.; Rogatko, A.; Xu, Z.; Hoffman, J.P.; Weiner, L.M.; Cheng, J.D. Fibroblast Activation Protein and Its Relationship to Clinical Outcome in Pancreatic Adenocarcinoma. Pancreas 2008, 37, 154–158.
  24. Lo, A.; Li, C.-P.; Buza, E.L.; Blomberg, R.; Govindaraju, P.; Avery, D.; Monslow, J.; Hsiao, M.; Puré, E. Fibroblast activation protein augments progression and metastasis of pancreatic ductal adenocarcinoma. JCI Insight 2017, 2, e92232.
  25. Feig, C.; Jones, J.O.; Kraman, M.; Wells, R.J.; Deonarine, A.; Chan, D.S.; Connell, C.M.; Roberts, E.W.; Zhao, Q.; Caballero, O.L.; et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl. Acad. Sci. USA 2013, 110, 20212–20217.
  26. Gunderson, A.J.; Yamazaki, T.; Mccarty, K.; Phillips, M.; Alice, A.; Bambina, S.; Zebertavage, L.; Friedman, D.; Cottam, B.; Newell, P.; et al. Blockade of fibroblast activation protein in combination with radiation treatment in murine models of pancreatic adenocarcinoma. PLoS ONE 2019, 14, e0211117.
  27. Röhrich, M.; Loktev, A.; Wefers, A.K.; Altmann, A.; Paech, D.; Adeberg, S.; Windisch, P.; Hielscher, T.; Flechsig, P.; Floca, R.; et al. IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein–specific PET/CT. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 2569–2580.
  28. Li, C.; Wen, B.; Tian, Y.; Chen, J.; He, Y. 68Ga-FAPI PET/CT Findings in a Rare Presacral Myxopapillary Ependymoma. Clin. Nucl. Med. 2022, 47, 385–386.
  29. Gong, W.; Yang, X.; Li, L.; Ma, J.; Zhang, C. Elevated 68Ga-FAPI Uptake by Primary Benign Intraosseous Meningioma. Clin. Nucl. Med. 2022, 47, 994–995.
  30. Zhu, Y.; Wu, J.; Wang, Y.; Geng, J.; Zhang, C. Presacral Benign Schwannoma Mimics Malignancy on 18F-FDG and 68Ga-FAPI PET/CT. Clin. Nucl. Med. 2022, 47, 277–278.
  31. Leeman, J.E.; Li, J.-G.; Pei, X.; Venigalla, P.; Zumsteg, Z.S.; Katsoulakis, E.; Lupovitch, E.; McBride, S.M.; Tsai, C.J.; Boyle, J.O.; et al. Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques. JAMA Oncol. 2017, 3, 1487–1494.
  32. Castaldi, P.; Leccisotti, L.; Bussu, F.; Miccichè, F.; Rufini, V. Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma. Acta Otorhinolaryngol. Ital. 2013, 33, 1–8.
  33. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424.
  34. Boscolo-Rizzo, P.; Zorzi, M.; Del Mistro, A.; Da Mosto, M.C.; Tirelli, G.; Buzzoni, C.; Rugge, M.; Polesel, J.; Guzzinati, S. The evolution of the epidemiological landscape of head and neck cancer in Italy: Is there evidence for an increase in the incidence of potentially HPV-related carcinomas? PLoS ONE 2018, 13, e0192621.
  35. Alterio, D.; Marvaso, G.; Ferrari, A.; Volpe, S.; Orecchia, R.; Jereczek-Fossa, B.A. Modern radiotherapy for head and neck cancer. Semin. Oncol. 2019, 46, 233–245.
  36. Schwartz, D.L.; Harris, J.; Yao, M.; Rosenthal, D.I.; Opanowski, A.; Levering, A.; Ang, K.K.; Trotti, A.M.; Garden, A.S.; Jones, C.U.; et al. Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522. Int. J. Radiat. Oncol. Biol. Phys. 2015, 91, 721–729.
  37. Giesel, F.L.; Kratochwil, C.; Lindner, T.; Marschalek, M.M.; Loktev, A.; Lehnert, W.; Debus, J.; Jäger, D.; Flechsig, P.; Altmann, A.; et al. 68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. J. Nucl. Med. 2019, 60, 386–392.
  38. Gu, B.; Xu, X.; Zhang, J.; Ou, X.; Xia, Z.; Guan, Q.; Hu, S.; Yang, Z.; Song, S. The Added Value of 68Ga-FAPI PET/CT in Patients with Head and Neck Cancer of Unknown Primary with 18F-FDG–Negative Findings. J. Nucl. Med. 2022, 63, 875–881.
  39. Promteangtrong, C.; Siripongsatian, D.; Jantarato, A.; Kunawudhi, A.; Kiatkittikul, P.; Yaset, S.; Boonkawin, N.; Chotipanich, C. Head-to-Head Comparison of 68Ga-FAPI-46 and 18F-FDG PET/CT for Evaluation of Head and Neck Squamous Cell Carcinoma: A Single-Center Exploratory Study. J. Nucl. Med. 2022, 63, 1155–1161.
  40. Chen, Y.; Zheng, S.; Zhang, J.; Yao, S.; Miao, W. Pleural Metastasis of Papillary Thyroid Cancer Depicted by 68Ga-FAPI PET/CT. Clin. Nucl. Med. 2022, 47, 467–468.
  41. Wang, Z.; Tang, Y.; Tan, Y.; Wei, Q.; Yu, W. Cancer-associated fibroblasts in radiotherapy: Challenges and new opportunities. Cell Commun. Signal. 2019, 17, 47.
  42. Liu, T.; Han, C.; Wang, S.; Fang, P.; Ma, Z.; Xu, L.; Yin, R. Cancer-associated fibroblasts: An emerging target of anti-cancer immunotherapy. J. Hematol. Oncol. 2019, 12, 86.
  43. Röhrich, M.; Syed, M.; Liew, D.P.; Giesel, F.L.; Liermann, J.; Choyke, P.L.; Wefers, A.K.; Ritz, T.; Szymbara, M.; Schillings, L.; et al. 68Ga-FAPI-PET/CT improves diagnostic staging and radiotherapy planning of adenoid cystic carcinomas—Imaging analysis and histological validation. Radiother. Oncol. 2021, 160, 192–201.
  44. Syed, M.; Flechsig, P.; Liermann, J.; Windisch, P.; Staudinger, F.; Akbaba, S.; Koerber, S.A.; Freudlsperger, C.; Plinkert, P.K.; Debus, J.; et al. Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 2836–2845.
  45. Qin, C.; Liu, F.; Huang, J.; Ruan, W.; Liu, Q.; Gai, Y.; Hu, F.; Jiang, D.; Hu, Y.; Yang, K.; et al. A head-to-head comparison of 68Ga-DOTA-FAPI-04 and 18F-FDG PET/MR in patients with nasopharyngeal carcinoma: A prospective study. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 3228–3237.
  46. Yang, X.; You, Z.; Mou, C.; Hu, Z.; Liu, H. Esophagitis Mimicking Esophageal Cancer on 68Ga-FAPI PET/CT. Clin. Nucl. Med. 2021, 47, 279–280.
  47. Ballal, S.; Yadav, M.P.; Moon, E.S.; Rösch, F.; ArunRaj, S.T.; Agarwal, S.; Tripathi, M.; Sahoo, R.K.; Bal, C. First-in-Human Experience With 177Lu-DOTAGA.(SA.FAPi)2 Therapy in an Uncommon Case of Aggressive Medullary Thyroid Carcinoma Clinically Mimicking as Anaplastic Thyroid Cancer. Clin. Nucl. Med. 2022, 47, e444–e445.
  48. Ettinger, D.S.; Aisner, D.L.; Wood, D.E.; Akerley, W.; Bauman, J.; Chang, J.Y.; Chirieac, L.R.; D’Amico, T.A.; Dilling, T.J.; Dobelbower, M.; et al. NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 5.2018. J. Natl. Compr. Cancer Netw. 2018, 16, 807–821.
  49. Xu, G.; Zhao, L.; He, Z. Performance of Whole-Body PET/CT for the Detection of Distant Malignancies in Various Cancers: A Systematic Review and Meta-Analysis. J. Nucl. Med. 2012, 53, 1847–1854.
  50. Treglia, G.; Sadeghi, R.; Annunziata, S.; Lococo, F.; Cafarotti, S.; Bertagna, F.; Prior, J.O.; Ceriani, L.; Giovanella, L. Diagnostic Accuracy of 18F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A systematic review and meta-analysis. Acad. Radiol. 2014, 21, 11–20.
  51. Yi, C.A.; Shin, K.M.; Lee, K.S.; Kim, B.-T.; Kim, H.; Kwon, O.J.; Choi, J.Y.; Chung, M.J. Non–Small Cell Lung Cancer Staging: Efficacy Comparison of Integrated PET/CT versus 3.0-T Whole-Body MR Imaging. Radiology 2008, 248, 632–642.
  52. Loktev, A.; Lindner, T.; Mier, W.; Debus, J.; Altmann, A.; Jäger, D.; Giesel, F.; Kratochwil, C.; Barthe, P.; Roumestand, C.; et al. A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. J. Nucl. Med. 2018, 59, 1423–1429.
  53. Kratochwil, C.; Flechsig, P.; Lindner, T.; Abderrahim, L.; Altmann, A.; Mier, W.; Adeberg, S.; Rathke, H.; Röhrich, M.; Winter, H.; et al. 68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. J. Nucl. Med. 2019, 60, 801–805.
  54. Toloza, E.M.; Harpole, L.; Detterbeck, F.; McCrory, D.C. Invasive Staging of Non-small Cell Lung Cancer: A review of the current evidence. Chest 2003, 123, 157S–166S.
  55. Can, C.; Kepenek, F.; Kömek, H.; Gündoğan, C.; Kaplan, I.; Taşdemir, B.; Güzel, Y.; Agüloğlu, N.; Karaoğlan, H. Comparison of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT in patients with non-small cell lung cancer. Nucl. Med. Commun. 2022, 43, 1084–1091.
  56. Hao, B.; Wu, J.; Pang, Y.; Sun, L.; Chen, H. 68Ga-FAPI PET/CT in Assessment of Leptomeningeal Metastases in a Patient With Lung Adenocarcinoma. Clin. Nucl. Med. Mol. Imaging 2020, 45, 784–786.
  57. Wei, Y.; Cheng, K.; Fu, Z.; Zheng, J.; Mu, Z.; Zhao, C.; Liu, X.; Wang, S.; Yu, J.; Yuan, S. AlF-NOTA-FAPI-04 PET/CT uptake in metastatic lesions on PET/CT imaging might distinguish different pathological types of lung cancer. Eur. J. Nucl. Med. 2022, 49, 1671–1681.
  58. Ballal, S.; Yadav, M.P.; Moon, E.S.; Kramer, V.S.; Roesch, F.; Kumari, S.; Tripathi, M.; ArunRaj, S.T.; Sarswat, S.; Bal, C. Biodistribution, pharmacokinetics, dosimetry of Ga-DOTA.SA.FAPi, and the head-to-head comparison with F-FDG PET/CT in patients with various cancers. Eur. J. Nucl. Med. Mol. Imaging 2020, 48, 1915–1931.
  59. Li, Y.; Lin, X.; Li, Y.; Lv, J.; Hou, P.; Liu, S.; Chen, P.; Wang, M.; Zhou, C.; Wang, X. Clinical Utility of F-18 Labeled Fibroblast Activation Protein Inhibitor (FAPI) for Primary Staging in Lung Adenocarcinoma: A Prospective Study. Mol. Imaging Biol. 2022, 24, 309–320.
  60. Wang, L.; Tang, G.; Hu, K.; Liu, X.; Zhou, W.; Li, H.; Huang, S.; Han, Y.; Chen, L.; Zhong, J.; et al. Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the Evaluation of Advanced Lung Cancer. Radiology 2022, 303, 191–199.
  61. Wang, S.; Zhou, X.; Xu, X.; Ding, J.; Liu, T.; Jiang, J.; Li, N.; Zhu, H.; Yang, Z. Dynamic PET/CT Imaging of 68Ga-FAPI-04 in Chinese Subjects. Front. Oncol. 2021, 11, 651005.
  62. Wang, J.; Welch, K.; Wang, L.; Kong, F.-M. Negative Predictive Value of Positron Emission Tomography and Computed Tomography for Stage T1-2N0 Non–Small-Cell Lung Cancer: A Meta-Analysis. Clin. Lung Cancer 2012, 13, 81–89.
  63. Shang, Q.; Zhao, L.; Pang, Y.; Meng, T.; Chen, H. Differentiation of Reactive Lymph Nodes and Tumor Metastatic Lymph Nodes With 68Ga-FAPI PET/CT in a Patient With Squamous Cell Lung Cancer. Clin. Nucl. Med. 2022, 47, 458–461.
  64. Tang, W.; Wu, J.; Yang, S.; Wang, Q.; Chen, Y. Organizing Pneumonia With Intense 68Ga-FAPI Uptake Mimicking Lung Cancer on 68Ga-FAPI PET/CT. Clin. Nucl. Med. 2022, 47, 223–225.
  65. Konishi, J.; Yamazaki, K.; Tsukamoto, E.; Tamaki, N.; Onodera, Y.; Otake, T.; Morikawa, T.; Kinoshita, I.; Dosaka-Akita, H.; Nishimura, M. Mediastinal Lymph Node Staging by FDG-PET in Patients with Non-Small Cell Lung Cancer: Analysis of False-Positive FDG-PET Findings. Respiration 2003, 70, 500–506.
  66. Betancourt-Cuellar, S.L.; Carter, B.W.; Palacio, D.; Erasmus, J.J. Pitfalls and Limitations in Non–Small Cell Lung Cancer Staging. Semin. Roentgenol. 2015, 50, 175–182.
  67. Wu, J.; Wang, Y.; Liao, T.; Rao, Z.; Gong, W.; Ou, L.; Chen, Y.; Zhang, C. Comparison of the Relative Diagnostic Performance of Ga-DOTA-FAPI-04 and FDG PET/CT for the Detection of Bone Metastasis in Patients With Different Cancers. Front. Oncol. 2021, 11, 737827.
  68. Kömek, H.; Can, C.; Güzel, Y.; Oruç, Z.; Gündoğan, C.; Yildirim, Ö.A.; Kaplan, I.; Erdur, E.; Yıldırım, M.S.; Çakabay, B. 68Ga-FAPI-04 PET/CT, a new step in breast cancer imaging: A comparative pilot study with the 18F-FDG PET/CT. Ann. Nucl. Med. 2021, 35, 744–752.
  69. Huang, Y.; Simms, A.E.; Mazur, A.; Wang, S.; León, N.R.; Jones, B.; Aziz, N.; Kelly, T. Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin. Exp. Metastasis 2011, 28, 567–579.
  70. Garin-Chesa, P.; Old, L.J.; Rettig, W.J. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc. Natl. Acad. Sci. USA 1990, 87, 7235–7239.
  71. Hua, X.; Yu, L.; Huang, X.; Liao, Z.; Xian, Q. Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma. Diagn. Pathol. 2011, 6, 111.
  72. Park, C.K.; Jung, W.H.; Koo, J.S. Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma. Breast Cancer Res. Treat. 2016, 159, 55–69.
  73. Jung, Y.Y.; Lee, Y.K.; Koo, J.S. Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer. Tumor Biol. 2015, 36, 8685–8695.
  74. Gong, C.; Nie, Y.; Qu, S.; Liao, J.-Y.; Cui, X.; Yao, H.; Zeng, Y.; Su, F.; Song, E.; Liu, Q. miR-21 Induces Myofibroblast Differentiation and Promotes the Malignant Progression of Breast Phyllodes Tumors. Cancer Res. 2014, 74, 4341–4352.
  75. Yin, J.J.; Pollock, C.B.; Kelly, K. Mechanisms of cancer metastasis to the bone. Cell Res. 2005, 15, 57–62.
  76. Mundy, G. Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2002, 2, 584–593.
  77. D’Oronzo, S.; Coleman, R.; Brown, J.; Silvestris, F. Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management. J. Bone Oncol. 2019, 15, 100205.
  78. Pang, Y.; Zhao, L.; Luo, Z.; Hao, B.; Wu, H.; Lin, Q.; Sun, L.; Chen, H. Comparison of 68Ga-FAPI and 18F-FDG Uptake in Gastric, Duodenal, and Colorectal Cancers. Radiology 2021, 298, 393–402.
  79. Li, M.; Younis, M.H.; Zhang, Y.; Cai, W.; Lan, X. Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: Cancer and beyond. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 2844–2868.
  80. Chen, H.; Pang, Y.; Wu, J.; Zhao, L.; Hao, B.; Wu, J.; Wei, J.; Wu, S.; Zhao, L.; Luo, Z.; et al. Comparison of Ga-DOTA-FAPI-04 and FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 1820–1832.
  81. Gong, W.; Chen, S.; He, L.; Liu, W.; Zhang, C. Intense 68Ga-FAPI Uptake in a Patient With Myositis Ossificans: Mimicking Bone Malignancy. Clin. Nucl. Med. 2022, 47, 638–639.
  82. Zheng, S.; Chen, Y.; Zhu, Y.; Yao, S.; Miao, W. Both Ga-FAPI and FDG PET/CT missed bone metastasis in a patient with breast cancer. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 4519–4520.
  83. Lindner, T.; Loktev, A.; Altmann, A.; Giesel, F.; Kratochwil, C.; Debus, J.; Jäger, D.; Mier, W.; Haberkorn, U. Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein. J. Nucl. Med. 2018, 59, 1415–1422.
  84. Dendl, K.; Finck, R.; Giesel, F.L.; Kratochwil, C.; Lindner, T.; Mier, W.; Cardinale, J.; Kesch, C.; Röhrich, M.; Rathke, H.; et al. FAP imaging in rare cancer entities—First clinical experience in a broad spectrum of malignancies. Eur. J. Nucl. Med. Mol. Imaging 2021, 49, 721–731.
  85. Koerber, S.A.; Finck, R.; Dendl, K.; Uhl, M.; Lindner, T.; Kratochwil, C.; Röhrich, M.; Rathke, H.; Ungerechts, G.; Adeberg, S.; et al. Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 3918–3924.
  86. Kessler, L.; Ferdinandus, J.; Hirmas, N.; Bauer, S.; Dirksen, U.; Zarrad, F.; Nader, M.; Chodyla, M.; Milosevic, A.; Umutlu, L.; et al. 68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial. J. Nucl. Med. 2022, 63, 89–95.
  87. Kratochwil, C.; Giesel, F.L.; Rathke, H.; Fink, R.; Dendl, K.; Debus, J.; Mier, W.; Jäger, D.; Lindner, T.; Haberkorn, U. Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 3011–3013.
  88. Ferdinandus, J.; Costa, P.F.; Kessler, L.; Weber, M.; Hirmas, N.; Kostbade, K.; Bauer, S.; Schuler, M.; Ahrens, M.; Schildhaus, H.-U.; et al. Initial clinical experience with 90Y-FAPI-46 radioligand therapy for advanced stage solid tumors: A case series of nine patients. J. Nucl. Med. 2022, 63, 727–734.
  89. Macpherson, R.E.; Pratap, S.; Tyrrell, H.; Khonsari, M.; Wilson, S.; Gibbons, M.; Whitwell, D.; Giele, H.; Critchley, P.; Cogswell, L.; et al. Retrospective audit of 957 consecutive 18F-FDG PET–CT scans compared to CT and MRI in 493 patients with different histological subtypes of bone and soft tissue sarcoma. Clin. Sarcoma Res. 2018, 8, 9.
  90. Charest, M.; Hickeson, M.; Lisbona, R.; Novales-Diaz, J.-A.; Derbekyan, V.; Turcotte, R.E. FDG PET/CT imaging in primary osseous and soft tissue sarcomas: A retrospective review of 212 cases. Eur. J. Nucl. Med. Mol. Imaging 2009, 36, 1944–1951.
  91. Lim, H.J.; Johnny Ong, C.-A.; Tan, J.W.-S.; Ching Teo, M.C. Utility of positron emission tomography/computed tomography (PET/CT) imaging in the evaluation of sarcomas: A systematic review. Crit. Rev. Oncol. Hematol. 2019, 143, 1–13.
  92. Gu, B.; Liu, X.; Wang, S.; Xu, X.; Liu, X.; Hu, S.; Yan, W.; Luo, Z.; Song, S. Head-to-head evaluation of FDG and Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 2889–2901.
  93. Ou, L.; Yang, X.; Liu, H.; Gong, W.; Zhang, C. Increased 68Ga-FAPI Activity in Malignant Melanoma of the Nasal Cavity. Clin. Nucl. Med. 2022, 47, 147–148.
  94. Mokoala, K.; Emil, N.; Lawal, I.; Antke, C.; Giesel, F.L.; Sathekge, M. Ga-FAPI versus F-FDG in malignant melanoma: Complementary or counterpoint? Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 2445–2446.
  95. Erol Fenercioğlu, O.; Beyhan, E.; Ergül, N.; Arslan, E.; Çermik, T.F. 18F-FDG PET/CT and 68Ga-FAPI-4 PET/CT Findings of Bilateral Knee Osteoarthritis in a Patient With Uveal Malignant Melanoma. Clin. Nucl. Med. 2022, 47, e144–e146.
  96. Lenz, G.; Wright, G.; Dave, S.S.; Xiao, W.; Powell, J.; Zhao, H.; Xu, W.; Tan, B.; Goldschmidt, N.; Iqbal, J.; et al. Stromal Gene Signatures in Large-B-Cell Lymphomas. N. Engl. J. Med. 2008, 359, 2313–2323.
  97. Augsten, M. Cancer-Associated Fibroblasts as Another Polarized Cell Type of the Tumor Microenvironment. Front. Oncol. 2014, 4, 62.
  98. Jin, X.; Wei, M.; Wang, S.; Wang, G.; Lai, Y.; Shi, Y.; Zhang, Y.; Yang, Z.; Wang, X. Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT. J. Nucl. Med. 2022, 63, 212–217.
  99. Kou, Y.; Yao, Z.M.; Cheng, Z. Hepatic Lesion of Mucosa-Associated Lymphoid Tissue Lymphoma Revealed by Al18F-NOTA-FAPI-04 PET/CT. Clin. Nucl. Med. 2022, 47, e49–e51.
  100. Zhang, Y.; Cai, J.; Lin, Z.; Yao, S.; Miao, W. Primary Central Nervous System Lymphoma Revealed by 68Ga-FAPI and 18F-FDG PET/CT. Clin. Nucl. Med. 2021, 46, e421–e423.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Yanzhao Dong
,
Hai-Ying Zhou
,
AHMAD ALHASKAWI
,
Zewei Wang
,
Jingtian Lai
,
Chengjun Yao
,
Zhenfeng Liu
,
SOHAIB HASAN ABDULLAH EZZI
,
Vishnu Goutham Kota
,
Mohamed Hasan Abdulla Hasan Abdulla
,
hui lu
View Times: 439
Revisions: 2 times (View History)
Update Date: 27 Feb 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback