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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 131 I-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 131 I-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 131 I-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., (© 2022. The Author(s).)

Background: Organ absorbed doses and effective doses can be used to compare radiation exposure among medical imaging procedures, compare alternative imaging options, and guide dose optimization efforts. Individual dose estimates are important for relatively radiosensitive patient populations such as children and for radiosensitive organs such as the eye lens. Software-based dose calculation methods conveniently calculate organ dose using patient-adjusted and examination-specific inputs., Methods: Organ absorbed doses and effective doses were calculated for 429 pediatric 18F-FDG PET-CT patients. Patient-adjusted and scan-specific information was extracted from the electronic medical record and scanner dose-monitoring software. The VirtualDose and OLINDA/EXM (version 2.0) programs, respectively, were used to calculate the CT and the radiopharmaceutical organ absorbed doses and effective doses. Patients were grouped according to age at the time of the scan as follows: less than 1 year old, 1 to 5 years old, 6 to 10 years old, 11 to 15 years old, and 16 to 17 years old., Results: The mean (+/- standard deviation, range) total PET plus CT effective dose was 14.5 (1.9, 11.2-22.3) mSv. The mean (+/- standard deviation, range) PET effective dose was 8.1 (1.2, 5.7-16.5) mSv. The mean (+/- standard deviation, range) CT effective dose was 6.4 (1.8, 2.9-14.7) mSv. The five organs with highest PET dose were: Urinary bladder, heart, liver, lungs, and brain. The five organs with highest CT dose were: Thymus, thyroid, kidneys, eye lens, and gonads., Conclusions: Organ and effective dose for both the CT and PET components can be estimated with actual patient and scan data using commercial software. Doses calculated using software generally agree with those calculated using dose conversion factors, although some organ doses were found to be appreciably different. Software-based dose calculation methods allow patient-adjusted dose factors. The effort to gather the needed patient data is justified by the resulting value of the characterization of patient-adjusted dosimetry.

Background: Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation., Methods: Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT., Results: In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times' difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs., Conclusions: VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.

Background: Whole body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the standard of care in oncologic diagnosis and staging, and patient radiation dose must be well understood to balance exam benefits with the risk from radiation exposure. Although reference PET/CT patient doses are available, the potential for widely varying total dose prompts evaluation of clinic-specific patient dose. The aims of this study were to use exam-specific information to characterize the radiation dosimetry of PET/CT exams that used two different CT techniques for adult oncology patients and evaluate the practicality of employing an exam-specific approach to dose estimation., Methods: Whole body PET/CT scans from two sets of consecutive adult patients were retrospectively reviewed. One set received a PET scan with a standard registration CT and the other a PET scan with a diagnostic quality CT. PET dose was calculated by modifying the standard reference phantoms in OLINDA/EXM 1.1 with patient-specific organ mass. CT dose was calculated using patient-specific data in ImPACT. International Commission on Radiological Protection publication 103 tissue weighting coefficients were used for effective dose., Results: One hundred eighty three adult scans were evaluated (95 men, 88 women). The mean patient-specific effective dose from a mean injected 18F-FDG activity of 450 ± 32 MBq was 9.0 ± 1.6 mSv. For all standard PET/CT patients, mean effective mAs was 39 ± 11 mAs, mean CT effective dose was 5.0 ± 1.0 mSv and mean total effective dose was 14 ± 1.3 mSv. For all diagnostic PET/CT patients, mean effective mAs was 120 ± 51 mAs, mean CT effective dose was 15.4 ± 5.0 mSv and mean total effective dose was 24.4 ± 4.3 mSv. The five organs receiving the highest organ equivalent doses in all exams were bladder, heart, brain, liver and lungs., Conclusions: Patient-specific parameters optimize the patient dosimetry utilized in the medical justification of whole body PET/CT referrals and optimization of PET and CT acquisition parameters. Incorporating patient-specific data into dose estimates is a worthwhile effort for characterizing patient dose, and the specific dosimetric information assists in the justification of risk and optimization of PET/CT.