Individualization of Radionuclide Therapies: Comparison
Please note this is a comparison between Version 4 by Jessie Wu and Version 3 by Jessie Wu.

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. 

  • internal dosimetry
  • radiopharmaceuticals
  • radionuclide therapy

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.
RadionuclideBasic Radiation

Type for

Therapy
Chemical and Dosage FormIndicationsAdministration RouteReferences
RadionuclideBasic Radiation

Type for Therapy
IndicationsReferences
Iodine 131IβSodium iodide
Yttrium 90YβThyroid carcinomaOral 
Breast cancer[35]Hyperthyroidism[12][13]
Lutetium 177LuβPancreatic cancer[36][37]Iodine 131Iβ PheochromocytomaIntravenous 
Iodine 131IβNeuroblastoma Central Nervous System/Leptomeningeal Metastases[38]IobenguaneParaganglioma
Phosphorus 32P[14][15]β[16][17]
Pancreatic cancer[39 Neuroblastoma

Carcinoid
 
Iodine 131IβApamistamabLeukemiaIntravenous[18]
Iodine 131IβTositumomabnon-Hodgkin’s lymphomaIntravenous[19][20]
Iodine 131IβLipiodolHCC, liver metastasisIntra-arterial

infusion
[21][22]Samarium 153SmβLexidronamPainful skeletal metastasesIntravenous[23]
Strontium 89SrβStrontium chloridePainful skeletal metastasesIntravenous[24]
Yttrium 90YβIbritumomabtiuxetannon-Hodgkin’s lymphomaIntravenous[25]
Yttrium 90Y

Therasphere
β90Y glass spheresUnresectable HCC

Liver metastasis
Intra-arterial

infusion
[26]
]
Copper 67CuβRadioimmunotherapy[40]
Holmium 166HoβHCC, liver metastasis[29]
Indium 111InAuger eGEP-NETs, lung and bladder cancer[41][42][43]
Tin 117mSnInternal conversion ePainful skeletal metastases[44]
Bismuth 213BiαGlioblastoma, prostate and bladder cancer[45][46][47]
Astatine 211AtALung cancer, glioblastoma, radioimmunotherapy[48][49][50][51]Yttrium 90Y

SIR-Spheres
β90Y resin spheresUnresectable 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 NETsIntravenous[28][29]
Lutetium 177Lu or Actinium225Acβ

α
[177Lu]Lu-PSMAProstate cancerIntravenous 
[225Ac]Ac-PSMA(mCRPC)[30][31]
Phosphorus 32P

Yttrium 90Y

Rhenium 186Re
βColloidsRadiosynovectomyIntra-articular

injection
[32]
Radium 223RaARadium dichloridePainful skeletal metastasesIntravenous[33][34]
RadionuclideBasic Radiation

Type for

Therapy
Chemical and Dosage FormIndicationsAdministration RouteReferences
HCC: hepatocellular carcinoma; SSTR2: Somatostatin receptor type 2; PSMA: prostate-specific membrane antigen; NET: neuroendocrine tumor; mCRPC: metastatic castration-resistant prostate cancer.
Table 2. Radionuclides currently introduced into radioisotope therapies, at the stage of research.
Radionuclides currently introduced into radioisotope therapies, at the stage of research.
RadionuclideBasic Radiation

Type for Therapy
IndicationsReferences
Iodine 131IβSodium iodideThyroid carcinoma
Yttrium 90YβBreast cancerOral[34 
]Hyperthyroidism[11
Lutetium 177Lu][12]
βPancreatic cancer[35]Iodine 131Iβ 
Iodine 131PheochromocytomaIIntravenous 
βNeuroblastoma Central Nervous System/Leptomeningeal Metastases[36]IobenguaneParaganglioma[13][14][15][16]
 Neuroblastoma

Carcinoid
 
Iodine 131
Phosphorus 32PβPancreatic cancer[37]IβApamistamabLeukemiaIntravenous[17]
Iodine 131IβTositumomab
Copper 67CuβRadioimmunotherapy[38]
Holmium 166HoβHCC, liver metastasis[non-Hodgkin’s lymphomaIntravenous[18][19]
39]
Indium 111InAuger eGEP-NETs, lung and bladder cancer[40Iodine 131IβLipiodolHCC, liver metastasisIntra-arterial

infusion
[20][21]
][41][42]
Tin 117mSnInternal conversion ePainful skeletal metastases[43]Samarium 153SmβLexidronamPainful skeletal metastases
Bismuth 213BiIntravenousαGlioblastoma, prostate and bladder cancer[44][45][46[22]
]Strontium 89SrβStrontium chloridePainful skeletal metastasesIntravenous[23]
Astatine 211AtALung cancer, glioblastoma, radioimmunotherapy[47][48][49][50]Yttrium 90YβIbritumomabtiuxetannon-Hodgkin’s lymphomaIntravenous[24]
Yttrium 90Y

Therasphere
β90Y glass spheresUnresectable HCC

Liver metastasis
Intra-arterial

infusion
[25]
Yttrium 90Y

SIR-Spheres
β90Y resin spheresUnresectable 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 NETsIntravenous[27][28]
Lutetium 177Lu or Actinium225Acβ

α
[177Lu]Lu-PSMAProstate cancerIntravenous 
[225Ac]Ac-PSMA(mCRPC)[29][30]
Phosphorus 32P

Yttrium 90Y

Rhenium 186Re
βColloidsRadiosynovectomyIntra-articular

injection
[31]
Radium 223RaARadium dichloridePainful skeletal metastasesIntravenous[32][33]
GEP-NET: gastroenteropancreatic neuroendocrine tumor; EC: electron capture.

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