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Unlabelled: A dosimetric analysis was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) and radiochemotherapeutic drugs [(188)Re-doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as evaluated in mice. Methods: Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), (188)Re-liposome, and (188)Re-DXR-liposome were obtained for the estimation of absorbed doses in tumors and normal organs. Two colon carcinoma mouse models were employed: subcutaneous growing solid tumor and malignant ascites pervading tumor models. Radiation-dose estimates for normal tissues and tumors were calculated by using the OLINDA/EXM program. An evaluation of a recommended maximum administered activity (MAA) for the nanotargeted drugs was also made. Results: Mean absorbed doses derived from (188)Re-liposome and (188)Re-DXR-liposome in normal tissues were generally similar to those from (188)Re-BMEDA in intraperitoneal and intravenous administration. Tissue-absorbed dose in the liver was 0.24-0.40 and 0.17-0.26 (mGy/MBq) and in red marrow was 0.033-0.050 and 0.038-0.046 (mGy/MBq), respectively, for (188)Re-liposome and (188)Re-DXR-liposome. Tumor-absorbed doses for the nanotargeted (188)Re-liposome and (188)Re-DXR-liposome were higher than those of (188)Re-BMEDA for both routes of administration (4-26-fold). Dose to red marrow defined the recommended MAA. Conclusions: Our results suggest that radionuclide and chemoradiotherapeutic passive targeting delivery, using nanoliposomes as the carrier, is feasible and promising in systemic-targeted radionuclide therapy. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To analyze the effects of normal x-ray inspection, machine washing, and machine drying on thermoluminescent dosimeter (TLD) measurements during external individual monitoring and to provide suggestions for determining individual monitoring measurements under the mentioned abnormal situations. In this study, we focused on three abnormal situations: x-ray inspection, machine washing, and machine drying, which are common in external individual dose monitoring. We measured and compared the doses from TLD with and without 11, 23, 35, and 50 security checks. We used different radiation sources to expose the TLDs before or after machine washing with or without hot drying. The three radiation sources are natural background radiation, 137 Cs γ rays, and 320 kVp x-rays. We measured 20 TLDs for each situation. The average doses for the TLDs with 11, 23, 35, 50 security checks are 27.7 μGy, 59.7 μGy, 84.1 μGy, and 121.0 μGy, respectively. We measured an average dose of 2.5 μGy per exposure. The doses showed no significant difference between different times of washing with different radiation sources, natural background radiation, 137 Cs, or x-ray exposures. There was also no significant difference between the dose coming from the controlled group, drying at 60 °C and 90 °C for 1 h after exposure to 137 Cs γ rays and 320 kVp x-rays. The common machine drying under the temperature of 90 °C did not affect TLD measured doses., (Copyright © 2024 Health Physics Society.)

Introduction: The expression of alpha-five beta-three (αVβ3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVβ3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2',2"-{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [ 68 Ga]Ga, [ 177 Lu]Lu, and [ 225 Ac]Ac was optimized. The binding affinity (K d ) of DOTAGA-IAC for the αVβ3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [ 177 Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [ 68 Ga]Ga-DOTAGA-IAC and [ 18 F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [ 68 Ga]Ga-DOTAGA-IAC and [ 18 F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). K d and B max measurements were 15.02 nM and 417 fmol for αVβ3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [ 177 Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30-35 mins postadministration. Out of the cohort, [ 68 Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUV max ) of 3.94 ± 0.58 compared with [ 18 F]FDG (SUV max 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVβ3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [ 68 Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVβ3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy.

Abstract: The OLINDA/EXM version 2.0 personal computer code was created as an upgrade to the widely used OLINDA/EXM 1.0 and 1.1 codes. This paper documents the upgrades that were implemented. New decay data and anthropomorphic and biokinetic models were implemented in the software, and the software alpha and beta tested. Agreement of doses between the OLINDA/EXM codes 1 and 2 was very good. Use of the new anthropomorphic and biokinetic models results in understandable differences between the codes. Previous models were retained in the new code, and those results were identical to those in the previous code. OLINDA/EXM 2.0 represents an upgrade from version 1, with new modeling data recommended by the international community. It standardizes internal dose calculations for dose assessments in clinical trials with radiopharmaceuticals, theoretical calculations for existing pharmaceuticals, teaching, and other purposes., Competing Interests: The author receives royalties for distribution of the software; otherwise, there are no conflicts of interest., (Copyright © 2023 Health Physics Society.)

Background: Extrapolation of human absorbed doses (ADs) from biodistribution experiments on laboratory animals is used to predict the efficacy and toxicity profiles of new radiopharmaceuticals. Comparative studies between available animal-to-human dosimetry extrapolation methods are missing. We compared five computational methods for mice-to-human AD extrapolations, using two different radiopharmaceuticals, namely [ 111 In]CHX-DTPA-scFv78-Fc and [ 68 Ga]NODAGA-RGDyK. Human organ-specific time-integrated activity coefficients (TIACs) were derived from biodistribution studies previously conducted in our centre. The five computational methods adopted are based on simple direct application of mice TIACs to human organs (M1), relative mass scaling (M2), metabolic time scaling (M3), combined mass and time scaling (M4), and organ-specific allometric scaling (M5), respectively. For [ 68 Ga]NODAGA-RGDyK, these methods for mice-to-human extrapolations were tested against the ADs obtained on patients, previously published by our group. Lastly, an average [ 68 Ga]NODAGA-RGDyK-specific allometric parameter α new was calculated from the organ-specific biological half-lives in mouse and humans and retrospectively applied to M3 and M4 to assess differences in human AD predictions with the α = 0.25 recommended by previous studies., Results: For both radiopharmaceuticals, the five extrapolation methods showed significantly different AD results (p < 0.0001). In general, organ ADs obtained with M3 were higher than those obtained with the other methods. For [ 68 Ga]NODAGA-RGDyK, no significant differences were found between ADs calculated with M3 and those obtained directly on human subjects (H) (p = 0.99; average M3/H AD ratio = 1.03). All other methods for dose extrapolations resulted in ADs significantly different from those calculated directly on humans (all p ≤ 0.0001). Organ-specific allometric parameters calculated using combined experimental [ 68 Ga]NODAGA-RGDyK mice and human biodistribution data varied significantly. ADs calculated with M3 and M4 after the application of α new  = 0.17 were significantly different from those obtained by the application of α = 0.25 (both p < 0.001)., Conclusions: Available methods for mouse-to-human dosimetry extrapolations provided significantly different results in two different experimental models. For [ 68 Ga]NODAGA-RGDyK, the best approximation of human dosimetry was shown by M3, applying a metabolic scaling to the mouse organ TIACs. The accuracy of more refined extrapolation algorithms adopting model-specific metabolic scaling parameters should be further investigated., (© 2022. The Author(s).)

Competing Interests: The author declares no conflicts of interest.

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., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

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., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To determine if heparin labeled with 99m Technetium ( 99m Tc) could be an imaging probe to detect eosinophil-related inflammation in eosinophilic esophagitis and to determine the biodistribution and radiation dosimetry of 99m Tc-heparin oral administration using image-based dosimetry models with esophageal modeling., Methods: Freshly prepared 99m Tc-heparin was administered orally to 5 research subjects. Radioactivity was measured by whole-body scintigraphy and single-photon emission computed tomography during the 24 hours postadministration. Following imaging, endoscopic examination was performed. The biodistribution of esophageal radioactivity was compared with endoscopic findings, eosinophil counts in biopsy tissues, and immunostaining for eosinophil granule major basic protein-1 (eMBP1). These studies were conducted from July 1, 2013, until April 22, 2017., Results: Oral administration of 99m Tc-heparin was well tolerated in all 5 subjects. The entire esophagus could be visualized dynamically during oral administration. Bound esophageal radioactivity marked areas of inflammation as judged by endoscopy scores, by eosinophils per high power field and by localization of eMBP1 using immunostaining. Ninety percent of the radioactivity did not bind to the esophagus and passed through the gastrointestinal tract., Conclusion: The biodistribution of ingested 99m Tc-heparin is almost exclusively localized to the gastrointestinal tract. Radiation exposure was highest in the lower gastrointestinal tract and was comparable with other orally administered diagnostic radiopharmaceuticals. The use of swallowed 99m Tc-heparin may aid in assessing eosinophil-related inflammation in the esophagus., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

With the recent approval of 177 Lu-DOTATATE for use in gastroenteropancreatic neuroendocrine tumors, access to peptide receptor radionuclide therapy is increasing. Representatives from the North American Neuroendocrine Tumor Society and the Society of Nuclear Medicine and Molecular Imaging collaborated to develop a practical consensus guideline for the administration of 177 Lu-DOTATATE. In this paper, we discuss patient screening, maintenance somatostatin analog therapy requirements, treatment location and room preparation, drug administration, and patient release as well as strategies for radiation safety, toxicity monitoring, management of potential complications, and follow-up. Controversies regarding the role of radiation dosimetry are discussed as well. This document is designed to provide practical guidance on how to safely treat patients with this therapy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

The use of radioactive nanoparticles as imaging and therapeutic agents is increasing globally. Indeed, the use of these nanoparticles as perfect theranostic agent is highly anticipated in the pharmaceutical market. Among the radioactive nanoparticles, liposomes, solid lipid nanoparticles and polymeric nanoparticles are the most studied. However little information among adverse reactions, absorbed dose and correct dose to achieve the theranostic goal in a translational application is available. We developed a radioactive polymeric nanoparticle and calculated the absorbed dose in animal model (Wistar rats) using the OLINDA/EXM program. The results showed that some nanoparticle were uptake in five organs and minor elimination through the gastrointestinal and urinary pathways. The data corroborates the safe use in terms of blood-brain barrier and did not show high uptake by liver. The dosimetry data support the safe use of radioactive nanoparticles as theranostic agent. Graphical abstract ᅟ.

A compendium of about 100 radiopharmaceuticals, based on the OLINDA/EXM version 2.0 software, is presented. A new generation of voxel-based, realistic human computational phantoms developed by the RADAR committee of the Society of Nuclear Medicine and Molecular Imaging, based on 2007 recommendations of the International Commission on Radiological Protection, was used to develop the dose estimates, and the most recent biokinetic models were used as well. These estimates will be made available in electronic form and can be modified and updated as models are changed and as new radiopharmaceuticals are added., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

This article discusses issues regarding administration of radiopharmaceuticals to pregnant women. Standardized dose estimates and possible biological effects on the unborn child are presented. Current and future mathematical models (phantoms) are discussed. Standardized dose estimates for pregnant women at several stages of gestation based on the current generation of phantoms are given. Issues related to administration of radioiodines, particularly 131 I-NaI, are presented. Iodine concentrates in the fetal thyroid and therefore can give very high doses, even resulting in complete destruction of the fetal thyroid. Strategies for preventing unwanted administrations of radiopharmaceuticals to these patients, and for strategies for mitigating radiation doses, should an unwanted administration occur, are discussed., (Copyright © 2017. Published by Elsevier Ltd.)

Current standard values of fetal dosimetry deriving from 18 F-FDG injection in pregnant women are estimated from animal data. The present communication offers a revision of fetal dosimetry values calculated from recently published human data, in which fetal 18 F-FDG uptake was directly observed in vivo. The final doses were obtained from the observed time-integrated activity coefficients and a new generation of anthropomorphic voxel-based pregnancy phantoms., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumour lesions of lung cancer patients, as penetration of the blood-brain barrier is important for optimal therapeutic outcomes. Here we prepare both 11 C- and 18 F-isotopologues of lorlatinib to determine the biodistribution and whole-body dosimetry assessments by positron emission tomography (PET). Non-traditional radiolabelling strategies are employed to enable an automated multistep 11 C-labelling process and an iodonium ylide-based radiofluorination. Carbon-11-labelled lorlatinib is routinely prepared with good radiochemical yields and shows reasonable tumour uptake in rodents. PET imaging in non-human primates confirms that this radiotracer has high brain permeability.

Background: The estimation of organ doses and effective doses for children receiving CT examinations is of high interest. Newer, more realistic anthropomorphic body models can provide information on individual organ doses and improved estimates of effective dose., Materials and Methods: Previously developed body models representing 50th-percentile individuals at reference ages (newborn, 1, 5, 10 and 15 years) were modified to represent 10th, 25th, 75th and 90th height percentiles for both genders and an expanded range of ages (3, 8 and 13 years). We calculated doses for 80 pediatric reference phantoms from simulated chest-abdomen-pelvis exams on a model of a Philips Brilliance 64 CT scanner. Individual organ and effective doses were normalized to dose-length product (DLP) and fit as a function of body diameter., Results: We calculated organ and effective doses for 80 reference phantoms and plotted them against body diameter. The data were well fit with an exponential function. We found DLP-normalized organ dose to correlate strongly with body diameter (R 2 >0.95 for most organs). Similarly, we found a very strong correlation with body diameter for DLP-normalized effective dose (R 2 >0.99). Our results were compared to other studies and we found average agreement of approximately 10%., Conclusion: We provide organ and effective doses for a total of 80 reference phantoms representing normal-stature children ranging in age and body size. This information will be valuable in replacing the types of vendor-reported doses available. These data will also permit the recording and tracking of individual patient doses. Moreover, this comprehensive dose database will facilitate patient matching and the ability to predict patient-individualized dose prior to examination.

Data from the literature show that the fetal absorbed dose from 18 F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms., Methods: The 18 F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms., Results: The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively., Conclusion: Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18 F-FDG PET scan., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Introduction: Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy., Methods: To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB)., Results: The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established., Conclusions: [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Organ dose is essential for accurate estimates of patient dose from CT., Objective: To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest-abdomen-pelvis CT and investigate how these relate to patient size., Materials and Methods: We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F = 21:19; range 0.6-17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies., Results: We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R(2) > 0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R(2) = 0.95). Our results agreed with previous studies within 12% using similar scan parameters (e.g., bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters., Conclusion: Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation.

Previously, the authors developed a series of eight realistic digital mouse and rat whole body phantoms based on NURBS technology to facilitate internal and external dose calculations in various species of rodents. In this paper, two body phantoms of adult beagles are described based on voxel images converted to NURBS models. Specific absorbed fractions for activity in 24 organs are presented in these models. CT images were acquired of an adult male and female beagle. The images were segmented, and the organs and structures were modeled using NURBS surfaces and polygon meshes. Each model was voxelized at a resolution of 0.75 × 0.75 × 2 mm. The voxel versions were implemented in GEANT4 radiation transport codes to calculate specific absorbed fractions (SAFs) using internal photon and electron sources. Photon and electron SAFs were then calculated for relevant organs in both models. The SAFs for photons and electrons were compatible with results observed by others. Absorbed fractions for electrons for organ self-irradiation were significantly less than 1.0 at energies above 0.5 MeV, as expected for many of these small-sized organs, and measurable cross irradiation was observed for many organ pairs for high-energy electrons (as would be emitted by nuclides like 32P, 90Y, or 188Re). The SAFs were used with standardized decay data to develop dose factors (DFs) for radiation dose calculations using the RADAR Method. These two new realistic models of male and female beagle dogs will be useful in radiation dosimetry calculations for external or internal simulated sources.

An analysis is presented of the possible dosimetric consequences of various potential contamination events involving 223Ra dichloride (Xofigo), the FDA-approved therapeutic agent used in the treatment of bone metastases in patients with castration-resistant prostate cancer. Three exposure scenarios are considered: inhalation dose to an individual due to the hypothetical inhalation of 219Rn and its progeny assumed to be released into the air from a liquid spill on the floor, external dose from direct photon exposure of an individual assigned to clean up a spill, and skin dose to an individual should the liquid material come into contact with their skin. Doses from the first two scenarios were very small; 2.8 × 10(-3) mSv and 8.1 × 10(-4) mSv, respectively. Using extremely conservative assumptions, the skin dose was estimated to be 72 mSv; in a realistic scenario, this dose would likely be an order of magnitude or more lower. These doses are very small compared to regulatory limits, and good health physics practices likely to be employed in such incidents would lower them still further. The authors conclude that the medical use of Xofigo does not pose any significant radiation safety issue with respect to potential contamination events, even if multiple incidents might occur during the course of a year, since all worst-case potential contamination events considered in this study will not result in significant radiation exposures to workers.

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by (131)I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression.

Unlabelled: PET has been used to examine changes in neurotransmitter concentrations in the living brain. Pioneering PET studies on the dopamine system have used D2 and D3 receptor (D2/D3) antagonists such as (11)C-raclopride. However, more recently developed agonist radioligands have shown enhanced sensitivity to endogenous dopamine. A limitation of available agonist radioligands is that they incorporate the short-lived radioisotope (11)C. In the current study, we developed the (18)F-labeled D2/D3 receptor agonist (R)-(-)-2-(18)F-fluoroethoxy-N-n-propylnorapomorphine ((18)F-MCL-524)., Methods: In total, 10 PET measurements were conducted on 5 cynomolgus monkeys. Initially, the binding of (18)F-MCL-524 was compared with that of (11)C-MNPA in 3 monkeys. Second, the specificity of (18)F-MCL-524 binding was examined in pretreatment studies using raclopride (1.0 mg/kg) and d-amphetamine (1.0 mg/kg). Third, a preliminary kinetic analysis was performed using the radiometabolite-corrected arterial input function of the baseline studies. Finally, 2 whole-body PET measurements were conducted to evaluate biodistribution and radiation dosimetry after intravenous injection of (18)F-MCL-524., Results: (18)F-MCL-524 entered the brain and provided striatum-to-cerebellum ratios suitable for reliable quantification of receptor binding using the multilinear reference tissue model. Mean striatal nondisplaceable binding potential (BPND) values were 2.0 after injection of (18)F-MCL-524 and 1.4 after (11)C-MNPA. The ratio of the BPND values of (18)F-MCL-524 and (11)C-MNPA was 1.5 across striatal subregions. After administration of raclopride and d-amphetamine, the (18)F-MCL-524 BPND values were reduced by 89% and 56%, respectively. Preliminary kinetic analysis demonstrated that BPND values obtained with the 1-tissue- and 2-tissue-compartment models were similar to values obtained with the multilinear reference tissue model. Estimated radiation doses were highest for gallbladder (0.27 mSv/MBq), upper large intestine (0.19 mSv/MBq), and small intestine (0.17 mSv/MBq). The estimated effective dose was 0.035 mSv/MBq., Conclusion: The (18)F-labeled agonist (18)F-MCL-524 appears suitable for quantification of D2/D3 receptor binding in vivo, and the results encourage extension to human studies. The longer half-life of (18)F makes (18)F-MCL-524 attractive for studies on modulation of the dopamine concentration-for example, in combination with simultaneous measurement of changes in blood-oxygen-level-dependent signal using bimodal PET/functional MRI., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: (18)F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ((18)F-FPEB) is a potent and specific radioligand for the metabotropic glutamate receptor subtype 5 (mGluR5). Before undertaking clinical research studies with (18)F-FPEB, we performed studies of human radiation dosimetry., Methods: Serial whole-body scans were obtained in 9 healthy human subjects (5 men, 4 women) for 190-440 min after the intravenous administration of (18)F-FPEB. Radiation doses were estimated using the OLINDA/EXM software., Results: Peak organ doses were to the urinary bladder wall, 0.258 mGy/MBq (0.955 rad/mCi), and gallbladder wall, 0.193 mGy/MBq (0.716 rad/mCi). The effective dose was 0.025 mSv/MBq (0.0922 rem/mCi). The doses to the red marrow and spleen were 0.00797 mGy/MBq (0.0295 rad/mCi) and 0.00709 mGy/MBq (0.0262 rad/mCi), respectively. Reducing the urinary voiding interval to 60 or 90 min lowered the urinary bladder wall dose to 0.0885 mGy/MBq (0.327 rad/mCi) or 0.128 mGy/MBq (0.473 rad/mCi), respectively, and the effective dose to 0.0149 mSv/MBq (0.0551 rem/mCi) or 0.0171 mSv/MBq (0.0634 rem/mCi), respectively., Conclusion: Urinary voiding should be performed during (18)F-FPEB studies to minimize radiation exposure to research subjects., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

While it is commonly said that the benefits of the use of radiation in the healing arts far outweigh any potential risks, there has not been to date an attempt to quantify the numerical benefits of uses of medical radiation. Using the 'Linear, No-Threshold' (LNT) model of radiation carcinogenesis, many have provided numerical estimates of the risks of radiation exposure, sometimes in irresponsible ways. In this work, we show, through several selected examples, how the numerical benefits of medical radiation exposures indeed far outweigh any theoretical cancer risks. Choosing more invasive measures, there are known rates of complications that result in mortalities in the patient populations. We note these real risks in the selected examples and compare them to the theoretical risks of cancer predicted by the LNT model., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: A first-in-human phase 1 clinical study was performed on 12 healthy adults with a high-specific-activity carrier-free formulation of (123)I-iobenguane. Clinical data are presented on the behavior of this receptor-targeting imaging agent., Methods: Whole-body and thoracic planar and SPECT imaging were performed over 48 h for calculation of tissue radiation dosimetry and for evaluation of clinical safety and efficacy., Results: A reference clinical imaging database acquired over time for healthy men and women injected with high-specific-activity (123)I-iobenguane showed organ distribution and whole-body retention similar to those of conventional (123)I-iobenguane. The heart-to-mediastinum ratios for the high-specific-activity formulation were statistically higher than for conventional formulations, and the predicted radiation dosimetry estimations for some organs varied significantly from those based on animal distributions., Conclusion: Human normal-organ kinetics, radiation dosimetry, clinical safety, and imaging efficacy provide compelling evidence for the use of high-specific-activity (123)I-iobenguane.

Background: Florbetapir is one of several 18F-labeled amyloid plaque imaging tracers for positron emission tomography (PET). As the bio-distribution and radiation dose of PET tracers in human research are important for estimating the relative risks and benefits, a study was conducted to obtain this information on florbetapir., Methods: Nine cognitively normal subjects (six females and three males, age 58 ± 10 years, weight 81 ± 17 kg) received an intravenous bolus injection of 395 ± 27.9 MBq of florbetapir, and whole-body emission scans were performed over approximately 6 h. Computed tomography scans were acquired for attenuation correction. Volumes of interest (VOIs) for source organs including the brain, liver, lung, heart wall, and vertebrae were defined on the PET images. The VOIs of the gallbladder, urinary bladder, and large and small intestines were also defined. Using reference man organ volumes (ICRP 30), total activity was calculated per organ for each time point. The resultant time-activity curves (TACs) were fitted with constrained exponentials. Kinetic data were entered into OLINDA/EXM software to calculate dose estimates; the dynamic urinary bladder and ICRP 30 GI tract models were employed. The effective dose (ED) for each subject was estimated from the acquired data using the adult model., Results: The mean ED determined for nine healthy volunteers was 18.60 ± 4.26 μSv/MBq or 6.88 mSv for a 370-MBq dose. The organs that received the highest radiation absorbed doses were the gallbladder, upper large intestine, small intestine, liver, and urinary bladder at 143.0 ± 80.20, 74.50 ± 34.20, 65.50 ± 29.60, 64.40 ± 22.10, and 27.10 ± 11.70 μSv/MBq, respectively., Conclusions: The ED for florbetapir has been calculated for nine healthy volunteers. At a dose of 370 MBq florbetapir, the total average ED is approximately 6.88 mSv.

This article discusses issues regarding administration of radiopharmaceuticals to pregnant women or nursing mothers. Uncertainties in calculated dose estimates and possible biological effects on the unborn child are presented. Models and dose estimates for pregnant women at several stages of gestation are given; the radionuclide of highest concern is (131)I-NaI due to its affinity for the fetal thyroid and the potentially high fetal thyroid doses. The article also reviews the extant literature regarding the expression of radiopharmaceuticals in breast milk, and suggested time periods for interruption of breast feeding after a nursing mother receives a radiopharmaceutical, if needed. Again, (131)I-NaI is often the radiopharmaceutical of most concern, for the same reasons in the nursing infant as were shown for the unborn child. Strategies for preventing unwanted administrations of radiopharmaceuticals to these patients are reviewed, with strategies for minimizing radiation doses where possible.

In this study, (123)I-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately., (© 2013 Elsevier Ltd. All rights reserved.)