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.

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.

Monitoring the biodistribution of radiolabeled therapeutics in mice.

Radiopharmaceutical therapy is a rapidly growing field for the treatment of cancer due to its high specificity and ability to target individual affected cells. A key component of the pre-clinical development of a new therapeutic radiopharmaceutical is the determination of its time-dependent distribution in tumors, normal tissues, and the whole body in mouse tumor models. Here, we provide an overview of the available instrumentation for the novice in radiation measurement. We also detail the methodology for assessing distribution and kinetics of a radiopharmaceutical and calculating radiation absorbed dose in mice using a gamma counter or a PET or SPECT camera.

Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action.

Drugs with a long residence time at their target sites are often more efficacious in disease treatment. The mechanism, however, behind prolonged retention at the site of action is often difficult to understand for non-covalent agents. In this context, we focus on epichaperome agents, such as zelavespib and icapamespib, which maintain target binding for days despite rapid plasma clearance, minimal retention in non-diseased tissues, and rapid metabolism. They have shown significant therapeutic value in cancer and neurodegenerative diseases by disassembling epichaperomes, which are assemblies of tightly bound chaperones and other factors that serve as scaffolding platforms to pathologically rewire protein-protein interactions. To investigate their impact on epichaperomes in vivo, we conducted pharmacokinetic and target occupancy measurements for zelavespib and monitored epichaperome assemblies biochemically in a mouse model. Our findings provide evidence of the intricate mechanism through which zelavespib modulates epichaperomes in vivo. Initially, zelavespib becomes trapped when epichaperomes bound, a mechanism that results in epichaperome disassembly, with no change in the expression level of epichaperome constituents. We propose that the initial trapping stage of epichaperomes is a main contributing factor to the extended on-target residence time observed for this agent in clinical settings. Zelavespib's residence time in tumors seems to be dictated by target disassembly kinetics rather than by frank drug-target unbinding kinetics. The off-rate of zelavespib from epichaperomes is, therefore, much slower than anticipated from the recorded tumor pharmacokinetic profile or as determined in vitro using diluted systems. This research sheds light on the underlying processes that make epichaperome agents effective in the treatment of certain diseases.

The risk index as a basis for risk/benefit analyses and protocol optimization in diagnostic nuclear imaging.

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.

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 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.

Efficacy of HER2-Targeted Intraperitoneal 225Ac α-Pretargeted Radioimmunotherapy for Small-Volume Ovarian Peritoneal Carcinomatosis.

Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide 225Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells. Here, we report the use of human epidermal growth factor receptor 2 (HER2) 225Ac-pretargeted radioimmunotherapy (PRIT) to treat a mouse model of human EOC SKOV3 xenografts growing as peritoneal carcinomatosis (PC). Methods: On day 0, 105 SKOV3 cells transduced with a luciferase reporter gene were implanted intraperitoneally in nude mice, and tumor engraftment was verified by bioluminescent imaging (BLI). On day 15, treatment was started using 1 or 2 cycles of 3-step anti-HER2 225Ac-PRIT (37 kBq/cycle as 225Ac-Proteus DOTA), separated by a 1-wk interval. Efficacy and toxicity were monitored for up to 154 d. Results: Untreated PC-tumor-bearing nude mice showed a median survival of 112 d. We used 2 independent measures of response to evaluate the efficacy of 225Ac-PRIT. First, a greater proportion of the treated mice (9/10 1-cycle and 8/10 2-cycle; total, 17/20; 85%) survived long-term compared with controls (9/27, 33%), and significantly prolonged survival was documented (log-rank [Mantel-Cox] P = 0.0042). Second, using BLI, a significant difference in the integrated BLI signal area to 98 d was noted between controls and treated groups (P = 0.0354). Of a total of 8 mice from the 2-cycle treatment group (74 kBq total) that were evaluated by necropsy, kidney radiotoxicity was mild and did not manifest itself clinically (normal serum blood urea nitrogen and creatinine). Dosimetry estimates (relative biological effectiveness-weighted dose, where relative biological effectiveness = 5) per 37 kBq administered for tumors and kidneys were 56.9 and 16.1 Gy, respectively. One-cycle and 2-cycle treatments were equally effective. With immunohistology, mild tubular changes attributable to α-toxicity were observed in both therapeutic groups. Conclusion: Treatment of EOC PC-tumor-bearing mice with anti-HER2 225Ac-PRIT resulted in histologic cures and prolonged survival with minimal toxicity. Targeted α-therapy using the anti-HER2 225Ac-PRIT system is a potential treatment for otherwise incurable EOC.

Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

PURPOSE: To evaluate the yttrium-90 (90Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure. MATERIALS AND METHODS: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after 90Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time 90Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of 90Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens' activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored. RESULTS: The mean measured 90Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal. CONCLUSIONS: Counting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing 90Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.

Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core-shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target-specific dual-modality imaging properties in a "hit and run" approach, this conjugate eradicated HER2-expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway-specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug-immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.

Radioimmunoscintigraphy and Pretreatment Dosimetry of 131I-Omburtamab for Planning Treatment of Leptomeningeal Disease.

Radiolabeled antibody treatment with 131I-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 131I-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 131I-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 131I-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 131I-omburtamab planar images had acceptable agreement with previously reported data determined from serial 124I-omburtamab PET scans.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

PURPOSE: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT. METHODS: Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis. RESULTS: All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED. CONCLUSION: For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.

Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

BACKGROUND: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies. PATIENTS AND METHODS: We conducted a phase I trial of intraventricular 131I-omburtamab using a standard 3 + 3 design. Eligibility criteria included adequate cerebrospinal fluid (CSF) flow, no major organ toxicity, and for patients > dose level 6, availability of autologous stem cells. Patients initially received 74 MBq radioiodinated omburtamab to evaluate dosimetry and biodistribution followed by therapeutic 131I-omburtamab dose-escalated from 370 to 2960 MBq. Patients were monitored clinically and biochemically for toxicity graded using CTCAEv 3.0. Dosimetry was evaluated using serial CSF and blood sampling, and serial PET or gamma-camera scans. Patients could receive a second cycle in the absence of grade 3/4 non-hematologic toxicity or progressive disease. RESULTS: Thirty-eight patients received 100 radioiodinated omburtamab injections. Diagnoses included metastatic neuroblastoma (n = 16) and other B7H3-expressing solid tumors (n = 22). Thirty-five patients received at least 1 cycle of treatment with both dosimetry and therapy doses. Acute toxicities included < grade 4 self-limited headache, vomiting or fever, and biochemical abnormalities. Grade 3/4 thrombocytopenia was the most common hematologic toxicity. Recommended phase 2 dose was 1850 MBq/injection. The median radiation dose to the CSF and blood by sampling was 1.01 and 0.04 mGy/MBq, respectively, showing a consistently high therapeutic advantage for CSF. Major organ exposure was well below maximum tolerated levels. In patients developing antidrug antibodies, blood clearance, and therefore therapeutic index, was significantly increased. In patients receiving cRIT for neuroblastoma, survival was markedly increased (median PFS 7.5 years) compared to historical data. CONCLUSIONS: cRIT with 131I-omburtamab is safe, has favorable dosimetry and may have a therapeutic benefit as adjuvant therapy for B7-H3-expressing leptomeningeal metastases. TRIAL REGISTRATION: clinicaltrials.gov NCT00089245, August 5, 2004.

Dosimetry in Radiopharmaceutical Therapy.

The application of radiopharmaceutical therapy for the treatment of certain diseases is well established, and the field is expanding. New therapeutic radiopharmaceuticals have been developed in recent years, and more are in the research pipeline. Concurrently, there is growing interest in the use of internal dosimetry as a means of personalizing, and potentially optimizing, such therapy for patients. Internal dosimetry is multifaceted, and the current state of the art is discussed in this continuing education article. Topics include the context of dosimetry, internal dosimetry methods, the advantages and disadvantages of incorporating dosimetry calculations in radiopharmaceutical therapy, a description of the workflow for implementing patient-specific dosimetry, and future prospects in the field.

Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma.

PURPOSE: Despite dramatic growth in the number of small-molecule drugs developed to treat solid tumors, durable therapeutic options to control primary central nervous system malignancies are relatively scarce. Chemotherapeutic agents that appear biologically potent in model systems have often been found to be marginally effective at best when given systemically in clinical trials. This work presents for the first time an ultrasmall (<8 nm) multimodal core-shell silica nanoparticle, Cornell prime dots (or C' dots), for the efficacious treatment of high-grade gliomas. EXPERIMENTAL DESIGN: This work presents first-in-kind renally clearable ultrasmall (<8 nm) multimodal C' dots with surface-conjugated doxorubicin (DOX) via pH-sensitive linkers for the efficacious treatment in two different clinically relevant high-grade glioma models. RESULTS: Optimal drug-per-particle ratios of as-developed nanoparticle-drug conjugates were established and used to obtain favorable pharmacokinetic profiles. The in vivo efficacy results showed significantly improved biological, therapeutic, and toxicological properties over the native drug after intravenous administration in platelet-derived growth factor-driven genetically engineered mouse model, and an EGF-expressing patient-derived xenograft (EGFR PDX) model. CONCLUSIONS: Ultrasmall C' dot-drug conjugates showed great translational potential over DOX for improving the therapeutic outcome of patients with high-grade gliomas, even without a cancer-targeting moiety.

F-18 meta-fluorobenzylguanidine PET imaging of myocardial sympathetic innervation.

BACKGROUND: I-123 meta-iodobenzylguanidine (MIBG) imaging has long been employed to noninvasively assess the integrity of human norepinephrine transporter-1 and, hence, myocardial sympathetic innervation. Positron-emitting F-18 meta-fluorobenzylguanidine (MFBG) has recently been developed for potentially superior quantitative characterization. We assessed the feasibility of MFBG imaging of myocardial sympathetic innervation. METHODS: 16 patients were imaged with MFBG PET (30-minute dynamic imaging of chest, followed by 3 whole-body acquisitions between 30 minutes and 4-hour post-injection). Blood kinetics were assessed from multiple samples. Pharmacokinetic modeling with reversible 1- and 2-compartment models was performed. Kinetic rate constants were re-calculated from truncated datasets. All patients underwent concurrent MIBG SPECT. RESULTS: MFBG myocardial uptake was rapid and sustained; the mean standardized uptake value (SUV (mean ± standard deviation)) was 5.1 ± 2.2 and 3.4 ± 1.9 at 1 hour and 3-4-hour post-injection, respectively. The mean K1 and distribution volume (VT) were 1.1 ± 0.6 mL/min/g and 34 ± 22 mL/cm3, respectively. Both were reproducible when re-calculated from truncated 1-hour datasets (Intraclass Correlation Coefficient of 0.99 and 0.91, respectively). Spearman's ϱ = 0.86 between MFBG SUV and VT and 0.80 between MFBG PET-derived VT and MIBG SPECT-derived heart-to-mediastinum activity concentration ratio. CONCLUSION: MFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation.

Intraperitoneal Pretargeted Radioimmunotherapy for Colorectal Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is considered incurable, and more effective therapies are needed. Herein we test the hypothesis that GPA33-directed intracompartmental pretargeted radioimmunotherapy (PRIT) can cure colorectal peritoneal carcinomatosis. Nude mice were implanted intraperitoneally with luciferase-transduced GPA33-expressing SW1222 cells for aggressive peritoneal carcinomatosis (e.g., resected tumor mass 0.369 ± 0.246 g; n = 17 on day 29). For GPA33-PRIT, we administered intraperitoneally a high-affinity anti-GPA33/anti-DOTA bispecific antibody (BsAb), followed by clearing agent (intravenous), and lutetium-177 (Lu-177) or yttrium-86 (Y-86) radiolabeled DOTA-radiohapten (intraperitoneal) for beta/gamma-emitter therapy and PET imaging, respectively. The DOTA-radiohaptens were prepared from S-2-(4-aminobenzyl)-1,4,7, 10-tetraazacyclododecane tetraacetic acid chelate (DOTA-Bn). Efficacy and toxicity of single- versus three-cycle therapy were evaluated in mice 26-27 days post-tumor implantation. Single-cycle treatment ([177Lu]LuDOTA-Bn 111 MBq; tumor dose: 4,992 cGy) significantly prolonged median survival (MS) approximately 2-fold to 84.5 days in comparison with controls (P = 0.007). With three-cycle therapy (once weekly, total 333 MBq; tumor dose: 14,975 cGy), 6/8 (75%) survived long-term (MS > 183 days). Furthermore, for these treated long-term survivors, 1 mouse was completely disease free (microscopic "cure") at necropsy; the others showed stabilized disease, which was detectable during PET-CT using [86Y]DOTA-Bn. Treatment controls had MS ranging from 42-52.5 days (P < 0.001) and 19/20 mice succumbed to progressive intraperitoneal disease by 69 days. Multi-cycle GPA33 DOTA-PRIT significantly prolongs survival with reversible myelosuppression and no chronic marrow (929 cGy to blood) or kidney (982 cGy) radiotoxicity, with therapeutic indices of 12 for blood and 12 for kidneys. MTD was not reached.

Biodistribution and Radiation Dosimetry of Intraperitoneally Administered 124I-Omburtamab in Patients with Desmoplastic Small Round Cell Tumors.

The aim of this study was to assess the pharmacokinetics, biodistribution, and radiation dosimetry of 124I-omburtamab administered intraperitoneally in patients with desmoplastic small round cell tumor. Methods: Eligible patients diagnosed with desmoplastic small round cell tumor with peritoneal involvement were enrolled in a phase I trial of intraperitoneal radioimmunotherapy with 131I-omburtamab. After thyroid blockade and before radioimmunotherapy, patients received approximately 74 MBq of 124I-omburtamab intraperitoneally. Five serial PET/CT scans were obtained up to 144 h after injection. Multiple blood samples were obtained up to 120 h after injection. Organ-absorbed doses were calculated with OLINDA/EXM. Results: Thirty-one patients were studied. Blood pharmacokinetics exhibited a biphasic pattern consisting of an initial rising phase with a median half-time (±SD) of 23 ± 15 h and a subsequent falling phase with a median half-time of 56 ± 34 h. Peritoneal distribution was heterogeneous and diffuse in most patients. Self-dose to the peritoneal cavity was 0.58 ± 0.19 mGy/MBq. Systemic distribution and activity in major organs were low. The median absorbed doses were 0.72 ± 0.23 mGy/MBq for liver, 0.48 ± 0.17 mGy/MBq for spleen, and 0.57 ± 0.12 mGy/MBq for kidneys. The mean effective dose was 0.31 ± 0.10 mSv/MBq. Whole-body and peritoneal cavity biologic half-times were 45 ± 9 and 24 ± 5 h, respectively. Conclusion: PET/CT imaging with intraperitoneally administered 124I-omburtamab enables assessment of intraperitoneal distribution and estimation of absorbed dose to peritoneal space and normal organs before therapy.