Functional recovery after macula involving retinal detachment and its correlation with preoperative biomarkers in optical coherence tomography.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1-G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1-G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.

A thermoluminescent method for the evaluation of the 131I effective half-life in the thyroid when treating Graves' disease.

When planning treatment for Graves' disease with 131I, the effective half-life (Teff) should be estimated individually as it depends on biological characteristics such as iodine uptake and excretion, which differ from an individual to another (Berg et al. 1996). All the methods to quantify Teff described in the literature are quite complex and are difficult to be used in clinical routine. With the aim of optimizing this process, a simplified method is proposed here to evaluate Teff of 131I during treatment of Graves' disease. The present study suggests improving the method of determining Teff based on thermoluminescence dosimetry. This involves implementing a new method and includes reduction of TLD (Thermoluminescent Dosimeter) measurements. The proposed method was validated on patients with Graves' disease. The radiation dose delivered to the patients was determined using the MIRD (Medical Internal Radiation Dosimetry) formalism. The relative difference between Teff obtained based on seven measurement intervals at [0-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h, 144-168 h] and based on three measurement intervals at [0-24 h, 72-96 h, 144-168 h] and [0-24 h, 120-144 h, 144-168 h] was 1.9% and 3.81%, respectively. Comparison of doses obtained based on a general Teff and on a personalized Teff gave a statistically significant difference with a correlation coefficient R2of 0.44. The Teff obtained from just three measurements was found to be sufficiently accurate and easily applicable. The results obtained demonstrate the need to determine and use personalized Teff values instead of using a fixed value of 7 days.

Voxel-Based Dosimetry of Iron Oxide Nanoparticle-Conjugated 177Lu-Labeled Folic Acid Using SPECT/CT Imaging of Mice.

Several radiolabeled folic acid conjugates have been developed for targeted imaging and therapy. However, the therapeutic concept with radiolabeled folate conjugates has not yet been applied to clinical applications owing to the high renal absorbed dose. The effectiveness of targeted radionuclide therapy (TRT) depends primarily on the absorbed dose rate and on the total absorbed dose delivered to the tumor and to normal tissue. Owing to various limitations associated with organ level dosimetry, voxel-based dosimetry has become essential for the assessment of a more  accurate absorbed dose during TRT. In this study, we synthesized iron oxide nanoparticle (IONP)-conjugated radiolabeled folate (177Lu-IONP-Folate) and performed voxel-based dosimetry using SPECT/CT images of normal mice through direct Geant4 application for emission tomography (GATE) Monte Carlo (MC) simulation. We also prepared 177Lu-Folate and 177Lu-IONPs for the comparison of absorbed doses with that of 177Lu-IONP-Folate. In addition, we calculated the mean absorbed dose at the organ-level using the medical internal radiation dose (MIRD) schema. The radioactivities of all three radiotracers were mainly accumulated in the liver and kidneys immediately after injection. For the kidneys, the voxel-based absorbed doses obtained with 177Lu-IONP-Folate, 177Lu-Folate, and 177Lu-IONPs were 1.01 ± 0.17, 2.46 ± 0.50, and 0.52 ± 0.08 Gy/MBq, respectively. The renal absorbed dose decreased significantly (∼half) when 177Lu-IONP-Folate was used compared with when the 177Lu-Folate only was used. The mean absorbed dose values obtained at organ-level using the MIRD schema were comparable to voxel-based absorbed doses estimated with GATE MC. The voxel-based absorbed dose values obtained in this study of individualized activity show that the renal absorbed dose could be reduced to almost half with 177Lu-IONP-Folate. Therefore, 177Lu-IONP-Folate could be clinically applicable in the TRT of folate receptor-positive cancers in a personalized manner when using the voxel-based dosimetry method.

Outpatient single-session yttrium-90 glass microsphere radioembolization.

PURPOSE: To investigate the feasibility of yttrium-90 ((90)Y) glass microsphere radioembolization (including angiography, lung shunt assessment, and treatment) as a single-session, outpatient procedure. MATERIALS AND METHODS: Between January 2008 and June 2013, 14 patients underwent outpatient, single-session radioembolization with (90)Y glass microspheres. As part of the routine diagnostic work-up, all patients underwent either computed tomography (CT) or magnetic resonance imaging of the liver with three-dimensional analysis and had laboratory results forwarded to our center for confirmation of candidacy before treatment. On treatment day, all patients underwent planning mesenteric angiography with flat panel cone-beam CT imaging. Patients were administered 33-85 MBq of technetium-99m macroaggregated albumin ((99m)Tc-MAA) via a microcatheter positioned in a hepatic artery supplying the tumor of interest. Planar scintigraphy was initiated within 2 hours after the administration of (99m)Tc-MAA and lung shunt fraction was determined. Final dosimetry calculations were performed while the patient was being transferred back from nuclear medicine to interventional radiology. RESULTS: All patients successfully underwent planning angiography with administration of (99m)Tc-MAA and (90)Y radioembolization as a single-session treatment. There were no reportable or recordable medical events; treatment was carried out to the desired dose in all cases. The mean total procedure time was 2.70 hours ± 0.72 (range, 1.63-3.97 h). CONCLUSIONS: This study reports a novel proof of concept for performing radioembolization in a single-session setting. By using the described method, time between initial clinical assessments and radioembolization treatment is decreased, and costs are minimized.

MIB Guides: Preclinical Radiopharmaceutical Dosimetry.

Preclinical dosimetry is essential for guiding the design of animal radiopharmaceutical biodistribution, imaging, and therapy experiments, evaluating efficacy and/or toxicities in such experiments, ensuring compliance with ethical standards for animal research, and, perhaps most importantly, providing reasonable initial estimates of normal-organ doses in humans, required for clinical translation of new radiopharmaceuticals. This MIB Guide provides a basic protocol for obtaining preclinical dosimetry estimates with organ-level dosimetry software.

MIRD Pamphlet No. 30: MIRDfit-A Tool for Fitting of Biodistribution Time-Activity Data for Internal Dosimetry.

In nuclear medicine, estimating the number of radioactive decays that occur in a source organ per unit administered activity of a radiopharmaceutical (i.e., the time-integrated activity coefficient [TIAC]) is an essential task within the internal dosimetry workflow. TIAC estimation is commonly derived by least-squares fitting of various exponential models to organ time-activity data (radiopharmaceutical biodistribution). Rarely, however, are methods used to objectively determine the model that best characterizes the data. Additionally, the uncertainty associated with the resultant TIAC is generally not evaluated. As part of the MIRDsoft initiative, MIRDfit has been developed to offer a biodistribution fitting software solution that provides the following essential features and advantages for internal dose assessment: nuclear medicine-appropriate fit functions; objective metrics for guiding best-fit selection; TIAC uncertainty calculation; quality control and data archiving; integration with MIRDcalc software for dose calculation; and a user-friendly Excel-based interface. For demonstration and comparative validation of MIRDfit's performance, TIACs were derived from serial imaging studies involving 18F-FDG and 177Lu-DOTATATE using MIRDfit. These TIACs were then compared with TIAC estimates obtained using other software. In most cases, the TIACs agreed within approximately 10% between MIRDfit and the other software. MIRDfit has been endorsed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging and has been integrated into the MIRDsoft suite of free dosimetry software; it is available for download at no user cost (https://mirdsoft.org/).

The MIRD Schema for Radiopharmaceutical Dosimetry: A Review.

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.

MIRD Pamphlet No. 29: MIRDy90-A 90Y Research Microsphere Dosimetry Tool.

90Y-microsphere radioembolization has become a well-established treatment option for liver malignancies and is one of the first U.S. Food and Drug Administration-approved unsealed radionuclide brachytherapy devices to incorporate dosimetry-based treatment planning. Several different mathematical models are used to calculate the patient-specific prescribed activity of 90Y, namely, body surface area (SIR-Spheres only), MIRD single compartment, and MIRD dual compartment (partition). Under the auspices of the MIRDsoft initiative to develop community dosimetry software and tools, the body surface area, MIRD single-compartment, MIRD dual-compartment, and MIRD multicompartment models have been integrated into a MIRDy90 software worksheet. The worksheet was built in MS Excel to estimate and compare prescribed activities calculated via these respective models. The MIRDy90 software was validated against available tools for calculating 90Y prescribed activity. The results of MIRDy90 calculations were compared with those obtained from vendor and community-developed tools, and the calculations agreed well. The MIRDy90 worksheet was developed to provide a vetted tool to better evaluate patient-specific prescribed activities calculated via different models, as well as model influences with respect to varying input parameters. MIRDy90 allows users to interact and visualize the results of various parameter combinations. Variables, equations, and calculations are described in the MIRDy90 documentation and articulated in the MIRDy90 worksheet. The worksheet is distributed as a free tool to build expertise within the medical physics community and create a vetted standard for model and variable management.

Internal absorbed dose calculation in body organs due to injection of Rhenium-188 labeled to Mu-9 antibody.

The use of radiopharmaceuticals has gained a special place in the diagnosis and treatment of cancers and evaluation of the function of different organs of the body. In this study, the absorbed dose distribution of organs after injection of 188Re-Mu-9 has been investigated using MIRD method and MCNP-4C simulation code. The 188Re-Mu-9 labeled was injected the mouse body and the amount of 188Re-labeled accumulation was evaluated after 1, 4 and 2 4 h. Having a map of the distribution of radiopharmaceutical activity in the animal body, it is possible to convert it into a human model to obtain the internal dose received by 188Re-Mu-9 injection using the MIRD calculation method and the MCNP simulation code. According to the results of the study, the animal/human model can be acceptable method for dose estimation of antibody-based radiopharmaceuticals.

MIRD Pamphlet No. 28, Part 2: Comparative Evaluation of MIRDcalc Dosimetry Software Across a Compendium of Diagnostic Radiopharmaceuticals.

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 128 radiopharmaceutical data compendium. Absorbed dose and effective dose coefficients were derived from the biokinetic datasets using MIRDcalc, IDAC-Dose, and OLINDA software. The dose coefficients obtained with MIRDcalc were systematically compared against the other software-derived dose coefficients and those originally presented in ICRP publication 128. Dose coefficients computed with MIRDcalc and IDAC-Dose showed excellent overall agreement. The dose coefficients derived from other software and the dose coefficients promulgated in ICRP publication 128 both were in reasonable agreement with the dose coefficients computed with MIRDcalc. Future work should expand the scope of the validation to include personalized dosimetry calculations.

Dosimetric evaluation of 123I (Iodide) and 99mTc (Pertechnetate) in the thyroid of neonates using Cristy-Eckerman and Segars anatomical representations.

Using the MIRD formalism, and the Cristy-Eckeman and Segars anthropomorphic representations, the absorbed dose in the thyroid of newborns, was calculated when 123I (iodide) and 99mTc (pertechnetate) are used during the diagnostic procedures. The dose results will allow exploring the dosimetric impact generated by the use of these radiopharmaceutical compounds and the use of two representations. Regardless the radiopharmaceutical compound and the anthropomorphic representation is the thyroid self-dose is the greatest, due to electrons emitted during the 123I and 99mTc radioisotopes. The relative difference in total dose to the newborn thyroid gland using the Cristy-Eckerman and Segars anthropomorphic representations for the compounds 123I(iodide) and 99mTc(pertechnetate) is 1.82%, and 1.33%, respectively. Regardless of the radiopharmaceutical compound, the replacement of Cristy-Eckerman by Segars phantom does not reflect significant changes in the estimated absorbed dose to the newborn thyroid. Regardless of the anthropomorphic representation, the lowest absorbed dose in newborn's thyroid is obtained when using 99mTc (pertechnetate) is used due to the residence times.

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

Fetal Dose from PET and CT in Pregnant Patients.

When pregnancy is discovered during or after a diagnostic examination, the physician or the patient may request an estimate of the radiation dose received by the fetus as per guidelines and standard operating procedures. This study provided the imaging community with dose estimates to the fetus from PET/CT with protocols that are adapted to University of Michigan low-dose protocols for patients known to be pregnant. Methods: There were 9 patients analyzed with data for the first, second, and third trimesters, the availability of which is quite rare. These images were used to calculate the size-specific dose estimate (SSDE) from the CT scan portion and the SUV and 18F-FDG uptake dose from the PET scan portion using the MIRD formulation. The fetal dose estimates were tested for correlation with each of the following independent measures: gestational age, fetal volume, average water-equivalent diameter of the patient along the length of the fetus, SSDE, SUV, and percentage of dose from 18F-FDG. Stepwise multiple linear regression analysis was performed to assess the partial correlation of each variable. To our knowledge, this was the first study to determine fetal doses from CT and PET images. Results: Fetal self-doses from 18F for the first, second, and third trimesters were 2.18 mGy (single data point), 0.74-1.82 mGy, and 0.017-0.0017 mGy, respectively. The combined SSDE and fetal self-dose ranged from 1.2 to 8.2 mGy. These types of images from pregnant patients are rare. Conclusion: Our data indicate that the fetal radiation exposure from 18F-FDG PET and CT performed, when medically necessary, on pregnant women with cancer is low. All efforts should be made to minimize fetal radiation exposure by modifying the protocol.

Internal dosimetry of 64Cu-DOX-loaded microcapsules by Monte Carlo method.

Some of the issues regarding introducing new radiocompounds in nuclear medicine are the distribution patterns, delivered dose to different organs, diagnostic abilities and side effects. In this study, in order to assess the biodistribution of 64Cu-DOX-loaded microcapsules, rats were IV-injected with the microcapsules, and 1, 4, 14, and 24 h later, the activities of the targeted organs were measured (%ID/g). The accumulated activities were achieved by %ID/g curves, and S-factors were obtained by MCNP outputs. The MIRD formulation and Monte Carlo method were used to determine the absorbed dose in the target organs. The biodistribution data and PET-CT images showed that the lungs were where the majority of activity was seen. According to MIRD and MCNP, the maximum dose delivered in the lungs was 5.79E+01 mGy/MBq and 4.70E+01 mGy/MBq, respectively. Also, the effective dose was 1.2E+01 for MIRD and 8.31E+00 mSv/MBq for MCNP. These results indicate that 64Cu-DOX microcapsules can be considered a new radiocompound in pulmonary imaging, and MCNP simulation can be a reliable method for internal dosimetry.

18F-alfatide II internal dosimetry using the ICRP 110 adult reference phantoms and the ICRP 103 tissue weighting factors.

PURPOSE: 18F-alfatide II is an arginine-glycine-aspartate (RGD) peptide-based PET tracer with promising imaging properties and pharmacokinetics. This study aims to calculate the absorbed and effective doses of 18F-alfatide II using the ICRP 110 adult reference phantoms and the ICRP 103 tissue weighting factors. METHODS: The MIRD method was used in this study to calculate the absorbed dose of organs and tissues. The biokinetic data were taken from a previous study. These data are based on the whole-body PET imaging of mice. RESULTS: The results show that the effective dose per unit activity administered of 18F-alfatide II is 1.33E-02 mSv/MBq. The urinary bladder wall receives the highest absorbed dose due to the administration of this radiopharmaceutical. Also, the effective dose of 18F-alfatide II is lower than that of 18F-FDG and some other RGD peptide-based tracers. CONCLUSIONS: Dose calculation using ICRP 110 voxelized adult reference phantoms and ICRP 103 tissue weighting factors leads to more realistic and accurate results for 18F-alfatide II compared to the stylized phantoms. The calculated effective dose of 18F-alfatide II in the present study is lower than that of previously published data.

A Realistic Multiregion Mouse Kidney Dosimetry Model to Support the Preclinical Evaluation of Potential Nephrotoxicity of Radiopharmaceutical Therapy.

Suborgan absorbed dose estimates in mouse kidneys are crucial to support preclinical nephrotoxicity analyses of α- and ß-particle-emitting radioligands exhibiting a heterogeneous activity distribution in the kidneys. This is, however, limited by the scarcity of reference dose factors (S values) available in the literature for specific mouse kidney tissues. Methods: A computational multiregion model of a mouse kidney based on high-resolution MRI data from a healthy mouse kidney was developed. The model was used to calculate S values for 5 kidney tissues (cortex, outer and inner stripes of outer medulla, inner medulla, and papilla and pelvis) for a wide range of ß- or α-emitting radionuclides (45 in total) of interest for radiopharmaceutical therapy, using Monte Carlo calculations. Additionally, regional S values were applied for a 131I-labeled single-domain antibody fragment with predominant retention in the outer stripe of the renal outer medulla. Results: The heterogeneous activity distribution in kidneys of considered α- and low- to medium-energy ß-emitters considerably affected the absorbed dose estimation in specific suborgan regions. The suborgan tissue doses resulting from the nonuniform distribution of the 131I-labeled antibody fragment largely deviated (from -40% to 57%) from the mean kidney dose resulting from an assumed uniform activity distribution throughout the whole kidney. The absorbed dose in the renal outer stripe was about 2.0 times higher than in the cortex and in the inner stripe and about 2.6 times higher than in inner tissues. Conclusion: The use of kidney regional S values allows a more realistic estimation of the absorbed dose in different renal tissues from therapeutic radioligands with a heterogeneous uptake in the kidneys. This constitutes an improvement from the simplistic (less accurate) renal dose estimates assuming a uniform distribution of activity throughout kidney tissues. Such improvement in dosimetry is expected to support preclinical studies essential for a better understanding of nephrotoxicity in humans. The dosimetric database has added value in the development of new molecular vectors for radiopharmaceutical therapy.

Dose-response Analysis in Hepatic Tumors Treated with 90Y-TARE According to a Personalized Dosimetric Workflow: Preliminary Results.

BACKGROUND: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off. METHODS: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values. RESULTS: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn't show sufficient classification capability for response or survival. CONCUSION: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.

An Analysis for Therapeutic Doses of Patients with Neuroendocrine Tumor Treated with Lutetium 177 (177Lu)-DOTATATE.

Background: The aim of this study is to clarify the critical organs that limit treatment scheme and also evaluate the validity of currently used critical organ threshold values in neuroendocrine tumor (NET) patients, receiving peptide receptor radionuclide therapy (PRRT) with Lutetium 177 (177Lu)-DOTATATE. Materials and Methods: Thirty-six NET patients (ages 16-73 years) who received 177Lu-DOTATATE treatment were evaluated retrospectively in this study. Dosimetric calculations were made using medical internal radionuclide dose method. For calculation of organ doses, Internal Dose Assessment at Organ Level/Exponential Modelling 1.1 software program was used. Follow-up data were used to determine the organ failure. Results: A total of 141 cycles and mean of 3.91 (±1.33) cycles were applied to the patients. A mean of 691 mCi (±257 mCi) 177Lu-DOTATATE infusion in total and a dose between 70 and 200 mCi per treatment was applied to patients. Seven of 36 patients reached 23 Gy renal dose limit. In these patients, although kidney doses were between 23 and 29 Gy, there was no diminution in renal functions during follow-up. Two of 36 patients reached total bone marrow dose of 2 Gy limit. Bone marrow suppression did not develop in these patients. Conclusion: The critical organs that seem to affect the treatment scheme in PRRT with 177Lu-DOTATATE are kidney and bone marrow. Although there are established threshold levels, derived from radiotherapy experience, more studies are needed to clarify these dose limits in systemic radionuclide therapies such as PRRT.

Internal dosimetry studies of 177Lu-BBN-GABA-DOTA, as a cancer therapy agent, in human tissues based on animal data.

The goal of using radiopharmaceuticals for therapeutic purposes is twofold: first, the most damage to cancer cells and, second, the most negligible dose transfers to healthy tissues. As 177Lu has the potential to cure a wide range of malignancies due to its varied range of beta energies, 177Lu-BBN-GABA-DOTA has been developed for therapeutic applications. In addition, 177Lu-BBN-GABA-DOTA can be over-expressed on gastrin-releasing peptide (GRP) receptors of the prostate, breast, small cell lung cancer, gastric, and colon tumors. The purpose of this study was to calculate the amount of dose absorption in human body organs using medical internal radiation dose (MIRD) and GATE code methods, after animal injection. In this study, the amount of absorbed dose in different organs (spleen, kidney, Lung, Pancreas, Heart, Adrenal, Intestine, Stomach, and Liver) were calculated for 1-MBq accumulation of 177Lu-BBN-GABA-DOTA in source organs (spleen, kidney, Lung, Pancreas, Heart, Adrenal, Intestine, Stomach, and Liver) using Monte Carlo Simulation (GATE code) with Zubal phantom. Moreover, compared with MIRD method, the results of the simulation showed considerable consistency. It was estimated that a 1-MBq administration of 177Lu-BBN-GABA-DOTA to the human body would result in an absorbed dose of 1.07E-02 mGy and 4.97E-02 (MIRD method) and 1.26E-02 mGy and 5.19E-02 (Gate code) in the Pancreas and adrenal 120 h after injection, respectively. The highest and lowest percentage differences between MIRD and Gate results are related to the Pancreas and spleen, respectively. Finally, the results showed that there is a good agreement between MIRD method and Gate code simulation for absorbed dose estimation.

Radiation Dosimetry of Theragnostic Pairs for Isotopes of Iodine in IAZA.

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.