Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease.

Background: Radiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic. Methods: Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 minutes, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+. Results: Post-administration exposure rates for patients ranged from 0.16-0.46 µSv/hr/MBq at 1 ft and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure duration ranged from 1-10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring. Conclusion: 131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.

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.

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.

Patient-specific radiological protection precautions following Cs collagen embedded Cs-131 implantation in the brain.

OBJECTIVE: Cesium-131 brachytherapy is an adjunct for brain tumor treatment, offering potential clinical and radiation protection advantages over other isotopes including iodine-125. We present evidence-based radiation safety recommendations from an initial experience with Cs-131 brachytherapy in the resection cavities of recurrent, previously irradiated brain metastases. METHODS: Twenty-two recurrent brain metastases in 18 patients were resected and treated with permanent Cs-131 brachytherapy implantation using commercially procured seed-impregnated collagen tiles (GammaTile, GT Medical Technologies). Exposure to intraoperative staff was monitored with NVLAP-accredited ring dosimeters. For patient release considerations, NCRP guidelines were used to develop an algorithm for modeling lifetime exposure to family and ancillary staff caring for patients based on measured dose rates. RESULTS: A median of 16 Cs-131 seeds were implanted (range 6-46) with median cumulative strength of 58.72U (20.64-150.42). Resulting dose rates were 1.19 mSv/h (0.28-3.3) on contact, 0.08 mSv/h (0.01-0.35) at 30 cm, and 0.01 mSv/h (0.001-0.03) at 100 cm from the patient. Modeled total caregiver exposure was 0.91 mSv (0.16-3.26), and occupational exposure was 0.06 mSv (0.02-0.23) accounting for patient self-shielding via skull and soft tissue attenuation. Real-time dose rate measurements were grouped into brackets to provide close contact precautions for caregivers ranging from 1-3 weeks for adults and longer for pregnant women and children, including cases with multiple implantations. CONCLUSIONS: Radiological protection precautions were developed based on patient-specific emissions and accounted for multiple implantations of Cs-131, to maintain exposure to staff and the public in accordance with relevant regulatory dose constraints.

SUBSTANTIAL EXTERNAL DOSE RATE VARIABILITY OBSERVED IN A COHORT OF LU-177 PATIENTS INDEPENDENT OF BMI AND SEX.

External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity, body mass index (BMI) and sex. The largest dose rate observed was 0.07 mSv/h associated with an administered activity of 7.2 GBq. Substantial variability was found in the distribution of the normalised dose rate associated that had an average of 0.0037 mSv/h per GBq and a 95% confidence interval of 0.0024-0.0058 mSv/h per GBq. Based on this study, estimating the patient dose rate based on the Lu-177 gamma exposure factor overestimates the dose rate by a factor of 2. A statistically significant inverse relationship was found between the patient dose rate and patient BMI and an empirically derived equation relating these two quantities was reported. On average, male patient dose rates were 3.5% lower than female dose rates, which may be attributed to the larger average BMI of the male patient group.

Radiation Safety Considerations and Clinical Advantages of α-Emitting Therapy Radionuclides.

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.α-emitting radionuclides provide an effective means of delivering large radiation doses to targeted treatment locations. 223RaCl2 is Food and Drug Administration-approved for treatment of metastatic castration-resistant prostate cancer, and 225Ac (225Ac-lintuzumab) radiolabeled antibodies have been shown to be beneficial for patients with acute myeloid leukemia. In recent years, there has been increasing use of α-emitters in theranostic agents with both small- and large-molecule constructs. The proper precautionary means for their use and surveying documentation of these isotopes in a clinical setting are an essential accompaniment to these treatments. Methods: Patient treatment data collected over a 3-y period, as well as regulatory requirements and safety practices, are described. Commonly used radiation instruments were evaluated for their ability to identify potential radioactive material spills and contamination events during a clinical administration of 225Ac. These instruments were placed at 0.32 cm from a 1.0-cm 225Ac disk source for measurement purposes. Radiation background values, efficiencies, and minimal detectable activities were measured and calculated for each type of detector. Results: The median external measured dose rate from 223RaCl2 patients (n = 611) was 2.5 µSv h-1 on contact and 0.2 µSv h-1 at 1 m immediately after administration. Similarly, 225Ac-lintuzumab (n = 19) patients had median external dose rates of 2.0 µSv h-1 on contact and 0.3 µSv h-1 at 1 m. For the measurement of 225Ac samples, a liquid scintillation counter was found to have the highest overall efficiency (97%), whereas a ZnS α-probe offered the lowest minimal detectable activity at 3 counts per minute. Conclusion: In this article, we report data from 630 patients who were undergoing treatment with the α-emitting isotopes 223Ra and 225Ac. Although α-emitters have the ability to deliver a higher internal radiation dose to the exposed tissues than can other unsealed radionuclides, they typically present minimal concerns about external dose rate. Additionally, α-radiation can be efficiently detected with appropriate radiation instrumentation, such as a liquid scintillation counter or ZnS probe, which should be prioritized when surveying for spills of α-emitters.

Attenuation of Gamma Radiation Using ClearView Radiation ShieldingTM in Nuclear Power Plants, Hospitals and Radiopharmacies.

Radiation protection materials, such as lead (Pb), water, concrete, steel, and aluminum, have been successfully used for decades. Although they are effective shields, these materials do have limitations. For example, lead is heavy and toxic, and water and concrete must be thick to provide significant shielding, all of which renders these materials prohibitive for certain applications. For example, the half-value layer for water to shield against Co is 30.48 cm (12"), which makes it an extremely bulky material. The development of ClearView Radiation Shielding addresses some of the limitations that are faced by traditional radiation protection shields. The product is a transparent liquid gamma radiation shield that can be fabricated in custom sizes and thicknesses. Here, we describe applications of ClearView Radiation Shielding in nuclear plants and hospitals. ClearView Radiation Shielding is used to shield nuclear power plant workers from Co in critical path and high dose in refueling outages to observe automated operations inside the containment, and operations such as cylindrical frisking stations and benchtop sampling. ClearView Radiation Shielding is designed as rolling shields and radionuclide containments in hospitals to protect staff and families during unsealed radionuclide treatment such as MIBG and Lutetium therapies. For successful implementation in hospitals, the product was tested against various radioisotopes, also described in this work. Operational uses of ClearView Radiation Shielding in commercial nuclear and medical industries allows staff working in radioactive environments visibility, better communication and similar levels of radiation protection compared with traditional shielding materials. The product helps improve workflows and reduced total dose received by workers. Additionally, attenuation measurements using ClearView Radiation Shielding against multiple isotopes was performed. With 1.25 cm (0.5") ClearView Radiation Shielding thickness, the shield attenuated 1) 65% of the effective dose from I, 2) 35.15% of the effective dose from Cs, and 3) 22.5% of the effective dose from Co. Isotopes in the range of 35 keV to 1899 keV. 3.81 were attenuated greater than 90% with a ClearView Radiation Shielding shield thickness of 7.62 cm (3"). The half-value layer for Co with a ClearView Radiation Shielding thickness of 3.81 cm (1.5") attenuated the effective dose of F gammas by 85.59%. With a density of 2.3 g cm, ClearView Radiation Shielding was measured to be half the weight of lead for equal shielding. ClearView Radiation Shielding is transparent, lightweight, and an alternative material to conventional radiation shields to reduce radiation exposure.

Radiological protection for pregnant women at a large academic medical Cancer Center.

PURPOSE: Most radiation protection programs, regulations and guidance apply specific restrictions to the occupational exposure of pregnant workers. The aim of this study was to compile data from the declared pregnant woman (DPW) radiation protection program over more than 5years at a large, high-volume, comprehensive oncology academic/medical institution and to evaluate for effectiveness against existing regulations and guidance. METHODS: A retrospective review was performed of the data collected as part of the DPW radiation protection program from January 2010 through May 2016, including the number of declared pregnancies, worker category, personal and fetal dosimetry monitoring measurements, workplace modifications, as well as the monthly and total recorded badge results during the entire pregnancy. RESULTS: 245 pregnancies were declared. The mean monthly fetal radiation dosimetry result was 0.009mSv with a median of 0.005mSv and a maximum of 0.39mSv. The mean total dose over the entire pregnancy was estimated to be 0.08mSv with a median of 0.05mSv and a maximum of 0.89mSv. Only 8 (3.2%) of the 245 declared pregnancies required that workplace modifications be implemented for the worker. CONCLUSIONS: The implementation of a declared pregnancy and fetal assessment program, careful planning, an understanding of the risks, and minimization of radiation dose by employing appropriate radiation safety measures as needed, can allow medical staff to perform procedures and normal activities without incurring significant risks to the conceptus, or significant interruptions of job activities for most medical workers.

Feasibility of Administering High-Dose (131) I-MIBG Therapy to Children with High-Risk Neuroblastoma Without Lead-Lined Rooms.

BACKGROUND: Although (131) I-metaiodobenzylguanidine ((131) I-MIBG) therapy is increasingly used for children with high-risk neuroblastoma, a paucity of lead-lined rooms limits its wider use. We implemented radiation safety procedures to comply with New York City Department of Health and Mental Hygiene regulations for therapeutic radioisotopes and administered (131) I-MIBG using rolling lead shields. PROCEDURE: Patients received 0.67 GBq (18 mCi)/kg/dose (131) I-MIBG on an IRB-approved protocol (NCT00107289). Radiation safety procedures included private room with installation of rolling lead shields to maintain area dose rates ≤0.02 mSv/hr outside the room, patient isolation until dose rate <0.07 mSv/hr at 1 m, and retention of a urinary catheter with collection of urine in lead boxes. Parents were permitted in the patient's room behind lead shields, trained in radiation safety principles, and given real-time radiation monitors. RESULTS: Records on 16 (131) I-MIBG infusions among 10 patients (age 2-11 years) were reviewed. Mean ± standard deviation (131) I-MIBG administered was 17.67 ± 11.14 (range: 6.11-40.59) GBq. Mean maximum dose rates outside treatment rooms were 0.013 ± 0.008 mSv/hr. Median time-to-discharge was 3 days post-(131) I-MIBG. Exposure of medical staff and parents was below regulatory limits. Cumulative whole-body dose received by the physician, nurse, and radiation safety officer during treatment was 0.098 ± 0.058, 0.056 ± 0.045, 0.055 ± 0.050 mSv, respectively. Cumulative exposure to parents was 0.978 ± 0.579 mSv. Estimated annual radiation exposure for inpatient nurses was 0.096 ± 0.034 mSv/nurse. Thyroid bioassay scans on all medical personnel showed less than detectable activity. Contamination surveys were <200 dpm/100 cm(2) . CONCLUSIONS: The use of rolling lead shields and implementation of specific radiation safety procedures allows administration of high-dose (131) I-MIBG and may broaden its use without dedicated lead-lined rooms.