Internal dosimetry evaluates the amount and spatial and temporal distributions of radiation energy deposited in tissue from radionuclides within the body. Historically, nuclear medicine had been largely a diagnostic specialty, and the implicitly performed risk-benefit analyses have been straightforward, with relatively low administered activities yielding important diagnostic information whose benefit far outweighs any potential risk associated with the attendant normal-tissue radiation doses. Although dose estimates based on anatomic models and population-average kinetics in this setting may deviate rather significantly from the actual normal-organ doses for individual patients, the large benefit-to-risk ratios are very forgiving of any such inaccuracies. It is in this context that the MIRD schema was originally developed and has been largely applied. The MIRD schema, created and maintained by the MIRD committee of the Society of Nuclear Medicine and Molecular Imaging, comprises the notation, terminology, mathematic formulas, and reference data for calculating tissue radiation doses from radiopharmaceuticals administered to patients. However, with the ongoing development of new radiopharmaceuticals and the increasing therapeutic application of such agents, internal dosimetry in nuclear medicine and the MIRD schema continue to evolve-from population-average and organ-level to patient-specific and suborgan to voxel-level to cell-level dose estimation. This article will review the basic MIRD schema, relevant quantities and units, reference anatomic models, and its adaptation to small-scale and patient-specific dosimetry.

Radioiodine therapy has been widely used for ablation of remnant tissue after a surgical procedure for treatment of differentiated thyroid carcinoma (DTC). The use of internal dosimetry procedures provides a new approach in choosing the activity to be administered considering the distribution and retention of 131I individually per patient. This study aims to assess the accumulated activity, internal bone marrow dosimetry and effective half-life of cases undergoing treatment for DTC. This is a quantitative retrospective study with analysis of diagnostic documents and images. The internal dosimetry method used consists of calculating the dose absorbed by the bone marrow per administered activity of 131I. The calculation of the absorbed dose takes into account the accumulated activity obtained through measurements of whole-body images acquired at 4 intervals over a period of 5 days. Dosimetry presented the values of absorbed dose per administered activity, with a mean of 0.101 mGy/MBq (min.: 0.042 - max.: 0.151). The mean whole-body residence time is equal to 23.1 hours (min: 12.6 - max: 39.4). Effective half-life equal to 16.0 hours (min.: 7.6 and max.: 28.2). Internal dosimetry provides information relevant to safe dose limits for application to DTC radioiodine therapy, especially in advanced cases of the disease where the use of greater activities may be necessary.

Imaging of cholesterol use is possible with the 131I scintiscanning/SPECT agent NP-59. This agent provided a noninvasive measure of adrenal function and steroid synthesis. However, iodine isotopes resulted in poor resolution, manufacturing challenges, and high radiation dosimetry to patients that have limited their use and clinical impact. A 18F analog would address these shortcomings while retaining the ability to image cholesterol use. The goal of this study was to prepare and evaluate a 18F analog of NP-59 to serve as a PET imaging agent for functional imaging of the adrenal glands based on cholesterol use. Previous attempts to prepare such an analog of NP-59 have proven elusive. Preclinical and clinical evaluation could be performed once the new fluorine analog of NP-59 production was established. Methods: The recent development of a new reagent for fluorination along with an improved route to the NP-59 precursor allowed for the preparation of a fluorine analog of NP-59, FNP-59. The radiochemistry for the 18F-radiolabeled 18F-FNP-59 is described, and rodent radiation dosimetry studies and in vivo imaging in New Zealand rabbits was performed. After in vivo toxicity studies, an investigational new drug approval was obtained, and the first-in-humans images with dosimetry using the agent were acquired. Results: In vivo toxicity studies demonstrated that FNP-59 is safe for use at the intended dose. Biodistribution studies with 18F-FNP-59 demonstrated a pharmacokinetic profile similar to that of NP-59 but with decreased radiation exposure. In vivo animal images demonstrated expected uptake in tissues that use cholesterol: gallbladder, liver, and adrenal glands. In this first-in-humans study, subjects had no adverse events and images demonstrated accumulation in target tissues (liver and adrenal glands). Manipulation of uptake was also demonstrated with patients who received cosyntropin, resulting in improved uptake. Conclusion: 18F-FNP-59 provided higher resolution images, with lower radiation dose to the subjects. It has the potential to provide a noninvasive test for patients with adrenocortical diseases.

Post-radioembolization lung absorbed dose verification was historically problematic and impractical in clinical practice. We devised an indirect method using yttrium-90 PET/CT. Conceptually, true lung activity is simply the difference between the total prepared activity minus all activity below the diaphragm and residual activity within delivery apparatus. Patient-specific lung mass is measured by CT densitovolumetry. True lung mean absorbed dose is calculated by MIRD macrodosimetry. Proof-of-concept is shown in a hepatocellular carcinoma patient with high lung shunt fraction 26%, where evidence of technically successful hepatic vein balloon occlusion for radioembolization lung protection was required. Indirect lung activity quantification showed the post-radioembolization lung shunt fraction to be reduced to approximately 1% with true lung mean absorbed dose approximately 1Gy, suggesting complete lung protection by hepatic vein balloon occlusion. We discuss possible clinical applications such as lung absorbed dose verification, refining the limits of lung tolerance and the concept of massive activity radioembolization.

Radioligand therapy applications for metastatic castration-resistant prostate cancer have been continuously rising in most nuclear medicine departments in Iran, but to our knowledge, no one has studied the doses of staff who perform treatment procedures. The current study aimed to determine the external radiation dose received by the staff of patients treated with 177Lu- prostate-specific membrane antigen therapy with and without a lead shield. This study used a dose ionization chamber to measure dose rates to the staff at various distances from patients and determined the average time spent by staff at these distances using an ionization chamber. Deep-dose equivalent to staff was obtained. The measured deep-dose equivalent to staff per patient was whitening the range of 1.8 to 5.2 mSv using a lead shield and 3.3 to 8.1 mSv without a lead shield. This study showed that a 2-mm lead shield markedly reduced the external dose to staff.It was indicated that the skill, accuracy, and speed of action of staff can directly affect their received dose.

Rationale: The aim of this study is to build a simulation framework to evaluate the number of DNA double strand breaks (DSBs) induced by in vitro targeted radionuclide therapy (TRT). This work represents the first step towards exploring underlying biological mechanisms and influence of physical/chemical parameters to enable a better response prediction in patients. We used this tool to characterize early DSB induction by [177Lu]Lu-DOTA-[Tyr3]octreotate (177Lu-DOTATATE), a commonly used TRT for neuroendocrine tumors. Methods: A multiscale approach is implemented to simulate the number of DSBs produced over 4 h by the cumulated decays of 177Lu distributed according the somatostatin receptor-binding. The approach involves 2 sequential simulations performed with Geant4/Geant4-DNA. The radioactive source is sampled according to uptake experiments on the distribution of activities within the medium and the planar cellular cluster, assuming instant and permanent internalization. A phase space (PHSP) is scored around the nucleus of the central cell. Then, the PHSP is used to generate particles entering the nucleus containing a multi-scale description of the DNA in order to score the number of DSBs per particle source. The final DSB computations are compared to experimental data, measured by immunofluorescent detection of 53BP1 foci. Results: The probability of electrons reaching the nucleus was significantly influenced by the shape of the cell compartment, causing large variance in the induction pattern of DSBs. A significant difference was found in the DSBs induced by activity distributions in cell and medium, which is explained by the specific energy (z) distributions. The average number of simulated DSBs is 14 DSBs/cell (range: 7-24 DSBs/cell) compared to 13 DSBs/cell (2-30) experimentally determined. We found a linear correlation between the mean absorbed dose to the nucleus and the number of DSBs/cell: 0.014 DSBs/cell mGy-1 for internalization in the Golgi apparatus and 0.017 DSBs/cell mGy-1 for internalization in the cytoplasm. Conclusion: This simulation tool can lead to more reliable absorbed dose to DNA correlation and help in prediction of biological response.

This paper presents standardized methods for collecting data to be used in performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. This document can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates, from animal or human data.

This paper presents standardized methods for performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. Special models for calculating time-activity integrals (urinary bladder, intestines) are also reviewed. This article can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates from animal or human data.

Tumor dosimetry was performed for 177Lu-DOTA-TATE with the aims of better understanding i) the range and variation of the tumor absorbed doses (ADs), ii) how different dosimetric quantities evolve over the treatment cycles, and iii) whether this evolution differs depending on the tumor grade. Such information is important for radiobiological interpretation and may inform the design of alternative administration schemes. Methods: Data come from 41 patients with neuroendocrine tumors (NETs) of grade 1 (n = 23) or 2 (n = 18), that had received between 2 and 9 treatment cycles. Dosimetry was performed for 182 individual lesions, giving in total 880 individual AD assessments across all cycles. Hybrid planar-SPECT/CT imaging was used, including quantitative SPECT reconstruction, voxel-based absorbed-dose-rate calculation, semi-automatic image segmentation, and partial-volume correction. Linear mixed-effect models were used to analyze changes over cycles in tumor ADs, absorbed-dose rates and activity concentrations at day-1, effective half-times, and tumor volumes. Tumors smaller than 8 ml were excluded from analyses. Results: Tumor ADs ranged between 2 and 77 Gy per cycle. On average the AD decreased over the cycles, with significantly different rates (P < 0.05) for grade 1 and 2 NETs of 6% and 14% per cycle, respectively. The absorbed-dose rates and activity concentrations at day-1 decreased by similar amounts. The effective half-times were less variable but shorter for grade 2 than grade 1 (P < 0.001). For grade 2 NETS the tumor volumes decreased, with a similar tendency in grade 1. Conclusion: The tumor AD, absorbed-dose rate and activity uptake decrease, in parallel with tumor volumes, between 177Lu-DOTA-TATE treatment cycles, particularly for grade 2 NETs. The effective half-times vary less but are lower for grade 2 than grade 1 NETs. These results may indicate the development of radiation-induced fibrosis and could have implications for the design of future treatment and dosimetry protocols.

The tumor-selective ganglioside antigene GD2 is frequently expressed on neuroblastomas and to a lesser extent also on sarcomas and neuroendocrine tumors. Aim of our study was to evaluate tumor targeting and biodistribution of iodine-131-labeled chimeric GD2-antibody clone 14/18 (131I-GD2-ch14.18) in patients with late-stage disease in order to identify eligibility for radioimmunotherapy. Methods: 20 patients (neuroblastoma n = 9; sarcoma n = 9; pheochromocytoma n = 1, neuroendocrine tumor n = 1) were involved in this study. 21 to 131 MBq (1-2 MBq/kg) of I-131-GD2-ch14.18 (0.5 -1.0 mg) were injected intravenously. Planar scintigraphy was performed within 1 h from injection (d0), on d1, d2, d3, and d6 or d7 to analyse tumor uptake and tracer biodistribution. Serial blood samples were collected in 4 individuals. Irradiation dose to tumor lesions and organs was calculated using Olinda® software. Results: The tumor targeting rate on a per-patient base was 65% (13/20) with 6/9 neuroblastomas showing uptake of I-GD2-ch14.18. Tumor lesions showed maximum uptake at 20-64 h p.i. (effective half-life in tumors 33-192 h). The tumor irradiation dose varied between 0.52 and 30.2 mGy/MBq (median: 9.08, n = 13). Visual analysis showed prominent blood pool activity up to d2/d3 p.i.. No pronounced uptake was observed in the bone marrow compartment or in the kidneys. Bone marrow dose was calculated at 0.07-0.47 mGy/MBq (median: 0.14) while blood dose was 1.1-4.7 mGy/MBq. Two patients (1 neuroblastoma and 1 pheochromocytoma) with particularly high tumor uptake underwent radioimmunotherapy using 2.3 and 2.9 GBq of I-GD2-ch14.18 both achieving stable disease. Overall survival was 17 and 6 months, respectively. Conclusion: I-GD2-ch14.18 is cleared slowly from blood resulting in good tumor to background contrast not until 2 d after application. With acceptable red marrow and organ dose, radioimmunotherapy is an option for patients with high tumor uptake. However, due to the variable GD2-expression, decision should be made depending on pretherapeutic dosimetry.