Evidence shows that better and more predictable outcomes can be achieved with patient-individualized dose assessment. Therefore, the incorporation of individual planning into radionuclide therapies is a high priority for nuclear medicine physicians and medical physicists alike. Internal dosimetry is used in tumor therapy to optimize the absorbed dose to the target tissue. For a nuclear medicine therapy to be considered personalized, treatment planning is essential, including the activity chosen individually for a given patient. The first step in individual planning of radioisotope therapy is to perform a series of diagnostic images, which allows visualizing the distribution and measuring how the activity decreased in time in different organs. The next step is to perform dosimetric measurements. It provides information on the degree of uptake of an administered radiopharmaceutical in pathological tissues and critical organs. The obtained dosimetric report is the foundation for planning the maximum activity on tumors, with a safe level of irradiation of critical organs in a given patient. The last step is to obtain a series of images of the patient recorded after the administration of the therapeutic radiopharmaceutical.
1. Introduction
Nuclear medicine uses radiopharmaceuticals, which are various molecules labeled with radioactive isotopes, for diagnosis and therapy. Radiopharmaceuticals are sources of radiation, and when introduced into the patient’s body (by injection, oral administration, or inhalation), they target specific organs, tissues, or cells. Subsequently, the activity of radiopharmaceuticals in tissues decreases due to their elimination from the body and radioactive decay. Administration of the same activity of a given radiopharmaceutical to different patients can distribute in their bodies differently, and therefore it is important to consider each patient individually. The determination of the total number of nuclear disintegrations that occur in a particular organ allows calculating the mean energy absorbed per kilogram of tissue. This parameter is known as the mean absorbed dose.
The knowledge of the absorbed ionizing radiation dose after administration of a radioactive preparation is of great importance both for the patient’s safety and for the proper course of diagnostics or radioisotope therapy. The activity of radioisotopes, administered to patients for diagnostic imaging studies, must ensure the correct image quality while minimizing the dose that will be absorbed. Due to the increase in sensitivity of modern gamma cameras, the reported diagnostic activities are low. However, in the case of radioisotope therapy, the activity of the therapeutic radioisotope should be as high as possible to effectively destroy tumor cells, and at the same time, low enough not to damage critical organs. Therapy using radioactive isotopes is an extremely important and rapidly developing part of nuclear medicine. Modern radioisotope treatments are based on the idea of theranostics
[1][2], according to which a diagnostic examination should be performed with the use of a radiopharmaceutical with the same distribution as the therapeutic radiopharmaceutical. Only when the result of the primary examination shows a sufficiently high accumulation of diagnostic radiopharmaceutical is the patient eligible for the treatment procedure.
In every clinical situation that requires the administration of a radioactive substance to the patient, it is important to know the absorbed dose. Moreover, it is of special importance when the activity is very high, as is the case with radioisotope therapies. Individualized therapy plans, created based on images of a given patient, allow for the optimization of therapy and the minimization of toxic effects
[2][3][4][5][6][7].
Both nuclear medicine and external beam radiotherapy (EBRT) use ionizing radiation to treat malignant tissue. EBRT requires advanced equipment that shapes the external beam to conform to the tumor, and nuclear medicine uses radiopharmaceuticals that are introduced directly into the body. Both treatment techniques should follow the guidelines contained in COUNCIL DIRECTIVE 2013/5/EURATOM from 5 December 2013, concerning the safety of patients diagnosed and treated with ionizing radiation
[78]. In Article 56 of the Directive, the following is written: “For all medical exposure of patients for radiotherapeutic purposes, exposures of target volumes shall be individually planned, and their delivery appropriately verified taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable and consistent with the intended radiotherapeutic purpose of the exposure.” This implies the necessity to personalize the treatment, i.e., the selection of the suitable pharmaceutical, in the right dosage and time. Individual EBRT planning is a common practice that has been developed and used for many years. Teams of physicists involved in treatment planning and clinical dosimetry for each and every patient are the standard in radiotherapy centers. Radiation treatment planning is performed with the use of advanced computer programs using computed tomography (CT), magnetic resonance (MR), or positron emission tomography (PET) images. Modern planning methods include the three-dimensional (3D) technique, which allows for the spatial shaping of radiation beams and the protection of critical organs
[89][910].
The situation in nuclear medicine is completely different. Few physicists work in nuclear medicine departments, and radioisotope therapies are usually performed according to standard clinical procedures. Individual calculations of radiopharmaceutical doses for patients are not routinely performed in most nuclear medicine facilities across the world. Nuclear medicine specialists most often use standard activities of radiopharmaceuticals during therapy, considering the patient’s weight or body surface area.
In some cases, administration of standard radiopharmaceutical activities does not provide a sufficiently high dose per tumor to destroy it. On the other hand, giving too much activity could have harmful effects on critical organs. A small fraction of patients receives optimal activity, while the vast majority receive lower doses. This conservative approach provides “radiation safety” to healthy tissues, but also delivers a lower dose than indicated to the neoplastic tissue, resulting in a low response rate and a higher rate of disease relapse. Individualized treatment planning would provide higher absorbed doses to most patients without risking toxicity. “Personalized dosimetry is a must for appropriate molecular radiotherapy”—this is the title of the article by Stabin (one of the pioneers of internal dosimetry) et al. published in 2019 in the
Medical Physics journal
[1011].
2. Radionuclides for Therapies
Due to the intensive development of pharmacology, the number of new radiopharmaceuticals that can be used in therapy is increasing every year. A particular advantage of radioisotope therapies is that they can be used in situations where all other forms of treatment have failed. Most radionuclides used in therapy emit β− particles, and rarely α particles, which are highly potent.
Table 1 contains information on the radionuclides used in radioisotope therapies.
Table 2, on the contrary, presents the radionuclides currently being tested, which provides the evidence of the intensive development of this method of treatment.
Table 1. Radionuclides used in particular types of radioisotope therapies.
Radionuclides used in particular types of radioisotope therapies.
Radionuclide |
Basic Radiation Type for Therapy |
Chemical and Dosage Form |
Indications |
Administration Route |
References |
Radionuclide |
Basic Radiation Type for Therapy |
Indications |
References |
Iodine 131I |
β− |
Sodium iodide |
Yttrium 90Y |
βThyroid carcinoma |
− | Oral |
|
Breast cancer |
[35] |
Hyperthyroidism |
[12][13] |
Lutetium 177Lu |
β− |
Pancreatic cancer |
[36][37] |
Iodine 131I |
β− |
|
Pheochromocytoma |
Intravenous |
|
Iodine 131I |
β− |
Neuroblastoma Central Nervous System/Leptomeningeal Metastases |
[38] |
Iobenguane |
Paraganglioma |
Phosphorus 32P | [14][15] |
β−[16][17] |
Pancreatic cancer |
[39 |
|
Neuroblastoma Carcinoid |
|
Iodine 131I |
β− |
Apamistamab |
Leukemia |
Intravenous |
[18] |
Iodine 131I |
β− |
Tositumomab |
non-Hodgkin’s lymphoma |
Intravenous |
[19][20] |
Iodine 131I |
β− |
Lipiodol |
HCC, liver metastasis |
Intra-arterial infusion |
[21][22] |
Samarium 153Sm |
β− |
Lexidronam |
Painful skeletal metastases |
Intravenous |
[23] |
Strontium 89Sr |
β− |
Strontium chloride |
Painful skeletal metastases |
Intravenous |
[24] |
Yttrium 90Y |
β− |
Ibritumomabtiuxetan |
non-Hodgkin’s lymphoma |
Intravenous |
[25] |
Yttrium 90Y Therasphere |
β− |
90Y glass spheres |
Unresectable HCC Liver metastasis |
Intra-arterial infusion |
[26] |
] |
Copper 67Cu |
β− |
Radioimmunotherapy |
[40] |
Holmium 166Ho |
β− |
HCC, liver metastasis |
[29] |
Indium 111In |
Auger e− |
GEP-NETs, lung and bladder cancer |
[41][42][43] |
Tin 117mSn |
Internal conversion e− |
Painful skeletal metastases |
[44] |
Bismuth 213Bi |
α |
Glioblastoma, prostate and bladder cancer |
[45][46][47] |
Astatine 211At |
A |
Lung cancer, glioblastoma, radioimmunotherapy |
[48][49][50][51] |
Yttrium 90Y SIR-Spheres |
β− |
90Y resin spheres |
Unresectable HCC Liver metastasis |
Intra-arterial infusion |
[27] |
Lutetium 177Lu or Yttrium 90Y |
β− |
[177Lu]Lu-DOTATATE [90Y]Y or [177Lu]Lu-DOTATOC |
Unresectable or metastasized NETs |
Intravenous |
[28][29] |
Lutetium 177Lu or Actinium225Ac |
β− α |
[177Lu]Lu-PSMA |
Prostate cancer |
Intravenous |
|
[225Ac]Ac-PSMA |
(mCRPC) |
[30][31] |
Phosphorus 32P Yttrium 90Y Rhenium 186Re |
β− |
Colloids |
Radiosynovectomy |
Intra-articular injection |
[32] |
Radium 223Ra |
A |
Radium dichloride |
Painful skeletal metastases |
Intravenous |
[33][34] |
Radionuclide |
Basic Radiation Type for Therapy |
Chemical and Dosage Form |
Indications |
Administration Route |
References |
Table 2. Radionuclides currently introduced into radioisotope therapies, at the stage of research.
Radionuclides currently introduced into radioisotope therapies, at the stage of research.
Radionuclide |
Basic Radiation Type for Therapy |
Indications |
References |
Iodine 131I |
β− |
Sodium iodide |
Thyroid carcinoma |
Yttrium 90Y |
β− |
Breast cancer | Oral |
[34 |
] |
Hyperthyroidism |
[11 |
Lutetium 177Lu][12] |
β− |
Pancreatic cancer |
[35] |
Iodine 131I |
β− |
|
Iodine 131 | Pheochromocytoma |
I | Intravenous |
|
β− |
Neuroblastoma Central Nervous System/Leptomeningeal Metastases |
[36] |
Iobenguane |
Paraganglioma |
[13][14][15][16] |
|
Neuroblastoma Carcinoid |
|
Iodine 131 |
Phosphorus 32P |
β− |
Pancreatic cancer |
[37] |
I |
β− |
Apamistamab |
Leukemia |
Intravenous |
[17] |
Iodine 131I |
β− |
Tositumomab |
Copper 67Cu |
β− |
Radioimmunotherapy |
[38] |
Holmium 166Ho |
β− |
HCC, liver metastasis |
[ |
non-Hodgkin’s lymphoma |
Intravenous |
[18][19] |
39 | ] |
Indium 111In |
Auger e− |
GEP-NETs, lung and bladder cancer |
[40 |
Iodine 131I |
β− |
Lipiodol |
HCC, liver metastasis |
Intra-arterial infusion |
[20][21] |
] | [ | 41 | ][42] |
Tin 117mSn |
Internal conversion e− |
Painful skeletal metastases |
[43] |
Samarium 153Sm |
β− |
Lexidronam |
Painful skeletal metastases |
Bismuth 213Bi | Intravenous |
α |
Glioblastoma, prostate and bladder cancer |
[44][45][46[22] |
] |
Strontium 89Sr |
β− |
Strontium chloride |
Painful skeletal metastases |
Intravenous |
[23] |
Astatine 211At |
A |
Lung cancer, glioblastoma, radioimmunotherapy |
[47][48][49][50] |
Yttrium 90Y |
β− |
Ibritumomabtiuxetan |
non-Hodgkin’s lymphoma |
Intravenous |
[24] |
Yttrium 90Y Therasphere |
β− |
90Y glass spheres |
Unresectable HCC Liver metastasis |
Intra-arterial infusion |
[25] |
Yttrium 90Y SIR-Spheres |
β− |
90Y resin spheres |
Unresectable HCC Liver metastasis |
Intra-arterial infusion |
[26] |
Lutetium 177Lu or Yttrium 90Y |
β− |
[177Lu]Lu-DOTATATE [90Y]Y or [177Lu]Lu-DOTATOC |
Unresectable or metastasized NETs |
Intravenous |
[27][28] |
Lutetium 177Lu or Actinium225Ac |
β− α |
[177Lu]Lu-PSMA |
Prostate cancer |
Intravenous |
|
[225Ac]Ac-PSMA |
(mCRPC) |
[29][30] |
Phosphorus 32P Yttrium 90Y Rhenium 186Re |
β− |
Colloids |
Radiosynovectomy |
Intra-articular injection |
[31] |
Radium 223Ra |
A |
Radium dichloride |
Painful skeletal metastases |
Intravenous |
[32][33] |