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Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124 I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124 I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124 I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124 I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124 I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124 I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

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., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Potential risk associated with low-dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk-related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging-appropriate risks factors including patient-specific size, age, and sex., Purpose: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure optimization, and support an evolution in the science of radiation risk assessment., Methods: In this study we describe, implement, and calculate RI for various diagnostic nuclear imaging scenarios using reference biokinetics published in ICRP Publication 128 for commonly utilized radiopharmaceuticals. All absorbed dose, E and RI calculations were performed using the freely available MIRDcalc nuclear medicine dosimetry software; the organ specific risk parameters used in the software are also benchmarked in this text. The resulting RI and E values are compared and various trends in RI values identified., Results: E and RI coefficients were calculated for 3016 use cases. Notably RI values vary depending on patient characteristics. Overall, across the population, global trends in RI values can be identified. In general, RI values were 2.15 times higher for females than males, due to higher risk coefficients and activities being distributed in smaller reference masses. The pediatric patients showed higher RIs than adults, as younger patients generally receive higher absorbed doses per administered activity, and are more radiosensitive, and have a longer projected lifespan at risk. A compendium of E and RI values is also provided in table format to serve as a reference for the community., Conclusions: RI is a rational quantity that could be used for justification, risk communication and protocol optimization in medical imaging. It has some advantages when compared to the long-utilized E value with respect to personalization, since accounts for patient size, age, sex, and natural incidence of cancer risk., (© 2023 American Association of Physicists in Medicine.)

Radiolabeled antibody treatment with 131 I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment 131 I-omburtamab imaging and dosimetric analysis in patients before therapy. Methods: Whole-body planar images were acquired 3 ± 1, 23 ± 2, and 47 ± 2 h after intracranioventricular administration of 75 ± 5 MBq of 131 I-omburtamab via an Ommaya reservoir. Multiple blood samples were also obtained for kinetic analysis. Separate regions of interest (ROIs) were manually drawn to include the lateral ventricles, entire spinal canal CSF space, and over the whole body. Count data in the ROIs were corrected for background and physical decay, converted to activity, and subsequently fitted to an exponential clearance function. The radiation absorbed dose was estimated to the CSF, separately to the spinal column and ventricles, and to the whole body and blood. Biodistribution of the injected radiolabeled antibody was assessed for all patients. Results: Ninety-five patients were included in the analysis. Biodistribution showed prompt localization in the ventricles and spinal CSF space with low systemic distribution, noted primarily as hepatic, renal, and bladder activity after the first day. Using ROI analysis, the effective half-lives were 13 ± 11 h (range, 5-75 h) for CSF in the spinal column, 8 ± 3 h (range, 3-17 h) for ventricles, and 41 ± 11 (range, 23-81 h) for the whole body. Mean absorbed doses were 0.63 ± 0.38 cGy/MBq (range, 0.24-2.25 cGy/MBq) for CSF in the spinal column, 1.03 ± 0.69 cGy/MBq (range, 0.27-5.15 cGy/MBq) for the ventricular CSF, and 0.45 ± 0.32 mGy/MBq (range, 0.05-1.43 mGy/MBq) for the whole body. Conclusion: Pretherapeutic imaging with 131 I-omburtamab allows assessment of biodistribution and dosimetry before the administration of therapeutic activity. Absorbed doses to the CSF compartments and whole body derived from the widely applicable serial 131 I-omburtamab planar images had acceptable agreement with previously reported data determined from serial 124 I-omburtamab PET scans., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Mesh-type and voxel-based computational phantoms comprise the current state of the art for internal dose assessment via Monte Carlo simulations but excel in different aspects, with mesh-type phantoms offering advantages over their voxel counterparts in terms of their flexibility and realistic representation of detailed patient- or subject-specific anatomy. We have developed PARaDIM (pronounced "paradigm": Particle and Heavy Ion Transport Code System-Based Application for Radionuclide Dosimetry in Meshes), a freeware application for implementing tetrahedral mesh-type phantoms in absorbed dose calculations. It considers all medically relevant radionuclides, including α, β, γ, positron, and Auger/conversion electron emitters, and handles calculation of mean dose to individual regions, as well as 3-dimensional dose distributions for visualization and analysis in a variety of medical imaging software. This work describes the development of PARaDIM, documents the measures taken to test and validate its performance, and presents examples of its uses. Methods: Human, small-animal, and cell-level dose calculations were performed with PARaDIM and the results compared with those of widely accepted dosimetry programs and literature data. Several tetrahedral phantoms were developed or adapted using computer-aided modeling techniques for these comparisons. Results: For human dose calculations, agreement of PARaDIM with OLINDA 2.0 was good-within 10%-20% for most organs-despite geometric differences among the phantoms tested. Agreement with MIRDcell for cell-level S value calculations was within 5% in most cases. Conclusion: PARaDIM extends the use of Monte Carlo dose calculations to the broader community in nuclear medicine by providing a user-friendly graphical user interface for calculation setup and execution. PARaDIM leverages the enhanced anatomic realism provided by advanced computational reference phantoms or bespoke image-derived phantoms to enable improved assessments of radiation doses in a variety of radiopharmaceutical use cases, research, and preclinical development. PARaDIM can be downloaded freely at www.paradim-dose.org., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: 16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer., Methods: Absorbed dose estimates were derived from 10 (18)F-FDHT PET studies (administered activity, 111-407 MBq) of 7 prostate cancer patients. Activity concentrations in plasma and red marrow (assuming a plasmacrit of 0.58, an extracellular fluid fraction of 0.40, and equilibration of activity between plasma and marrow extracellular fluid) were measured ex vivo from a peripheral blood sample. Liver, spleen, urinary bladder contents, and total-body activities were measured by region-of-interest analysis of quantitative whole-body studies acquired with a dedicated PET scanner. Total organ activities and residence times were calculated from the respective PET scan-derived activity concentrations assuming standard (70 kg) man organ masses. Urinary excretion was corrected for hepatobiliary excretion (liver activity), and a first-order adjustment was made for the bladder-wall mass based on the patient's total-body mass. Mean organ absorbed doses were calculated with the MIRD formalism and the standard man model using the MIRDOSE3 software program., Results: The absorbed doses (mean +/- SD) ranged from 0.00057 +/- 0.000281 cGy/MBq (to skin) to 0.00868 +/- 0.00481 cGy/MBq (to bladder wall) (voiding intervals, 1-2 h), and the effective dose equivalent was 0.00177 +/- 0.000152 cSv/MBq., Conclusion: The maximum absorbed dose among all tissues in all 10 studies, 0.0151 cGy/MBq, occurred for the urinary bladder wall (with hydration and 1- to 2-h voiding intervals). To ensure that the maximum normal-tissue absorbed dose is kept below the recommended maximum permissible dose of 5 cGy per single administration, a maximum administered activity of 331 MBq (5 cGy/[0.0151 cGy/MBq]) is recommended for (18)F-FDHT.

Internal dosimetry deals with the determination of the amount and the spatial and temporal distribution of radiation energy deposited in tissue by radionuclides within the body. Nuclear medicine has been largely a diagnostic specialty, and model-derived average organ dose estimates for risk assessment, the traditional application of the MIRD schema, have proven entirely adequate. However, to the extent that specific patients deviate kinetically and anatomically from the model used, such dose estimates will be inaccurate. With the increasing therapeutic application of internal radionuclides and the need for greater accuracy, radiation dosimetry in nuclear medicine is evolving from population- and organ-average to patient- and position-specific dose estimation. Beginning with the relevant quantities and units, this article reviews the historical methods and newly developed concepts and techniques to characterize radionuclide radiation doses. The latter include the 3 principal approaches to the calculation of macroscopic nonuniform dose distributions: dose point-kernel convolution, Monte Carlo simulation, and voxel S factors. Radiation dosimetry in "sensitive" populations, including pregnant women, nursing mothers, and children, also will be reviewed.

Accurate and precise radiation dosimetry is critical for the successful therapeutic application of systemically administered radionuclides, including, of course, radionuclides in the form of radiolabeled antibody. This requires determination, based on discrete serial measurements, of the time-dependent concentrations and/or total amounts of radioactivity in situ in order to calculate source region cumulated activities. Based on extensive studies (with clinically realistic numbers of counts and accuracies of the order of 10%) in simple geometric phantoms, in complex anthropomorphic phantoms, in animal models, and in humans, quantitative rotating scintillation camera-based single-photon emission computed tomography (SPECT) now appears to be a practical approach to such measurements. The basis of the quantitative imaging capability of a three-dimensional imaging modality such as SPECT is the elimination in the reconstructed image of counts emanating from activity surrounding the source region. Subject to considerations such as the reconstruction algorithm, attenuation and scatter corrections, and, most importantly, statistical uncertainty, the counts in a pixel in a reconstructed image are therefore directly proportional to the actual counts emanating from the corresponding voxel in situ. Among intrinsic, pre-processing, and post-processing attenuation corrections, post-processing algorithms, the most widely used approach in current commercial SPECT systems, have proven adequate in uniformly attenuating parts of the body (eg, abdomen, pelvis), subject to accurate delineation of the body contour. Although a number of sophisticated scatter correction methods have been developed, the lack of explicit scatter correction has, in practice, not been a major impediment to reasonably accurate quantitative SPECT imaging, despite scattered radiation representing up to 50% of the counts in a large source region (eg, liver). Because of its mathematical propagation in the image reconstruction process, statistical uncertainty (ie, "noise") in SPECT is far greater than would be expected if it were distributed according to Poisson statistics, as in planar imaging. The low "single slice" sensitivity of rotating scintillation camera-based SPECT is therefore the principal limitation of practical quantitative SPECT. Accordingly, absolute quantitation of count-limited clinical images has been accomplished using a judiciously selected "non-ramp" filter function. In summary, reasonable quantitative SPECT imaging is now feasible clinically, even without sophisticated scatter corrections, at least in uniformly attenuating parts of the body.(ABSTRACT TRUNCATED AT 400 WORDS)