Matthew J. Williamson

Unconventional nuclides for radiopharmaceuticals.

Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission tomography (PET) and 99mTc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of “nonstandard” radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including β+, β−−, γ-ray, and α-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy γ-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are discussed.

Fears, feelings, and facts: interactively communicating benefits and risks of medical radiation with patients.

OBJECTIVE As public awareness of medical radiation exposure increases, there has been heightened awareness among patients and physicians of the importance of holistic benefit-and-risk discussions in shared medical decision making. CONCLUSION We examine the rationale for informed consent and risk communication, draw on the literature on the psychology of radiation risk communication to increase understanding, examine methods commonly used to communicate radiation risk, and suggest strategies for improving communication about medical radiation benefits and risk.

RADIATION SAFETY CONSIDERATIONS FOR THE USE OF 223RaCl2 DE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER

AbstractThe majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (223RaCl2), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg−1 body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered 223Ra dichloride were typically less than 2 &mgr;Sv h−1 MBq−1 on contact and averaged 0.02 &mgr;Sv h−1 MBq−1 at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5–11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that 223Ra may provide a new standard of care for patients with CRPC and bone metastases.

Feasibility of ex Vivo FDG PET of the Colon1

To facilitate future direct correlations between fluorine 18 fluorodeoxyglucose (FDG)-avid colonic lesions and immunohistochemical assay findings, the authors tested the feasibility of ex vivo FDG positron emission tomography (PET) of the colon resected from humans. In this institutional review board-approved, HIPAA-compliant study, the authors, after obtaining informed patient consent, injected FDG intraoperatively in five patients with neoplasms and imaged their resected colons approximately 3 hours later. The colon could be imaged during this fairly limited time interval, and polyps and cancers could be identified. No biologic tissue degradation occurred. The authors concluded that ex vivo FDG PET of the colon is feasible and, when combined with careful histologic and immunohistochemical analyses, may serve as a research tool to determine the mechanisms of the normal colonic uptake of FDG and the localization of FDG in polyps and cancers.

Intraoperative high-dose rate of radioactive phosphorus 32 brachytherapy for diffuse recalcitrant conjunctival neoplasms: a retrospective case series and report of toxicity.

IMPORTANCE Adjunct treatments for conjunctival malignancies are needed when standard therapy provides limited benefits or fails. OBJECTIVE To describe the results of patients with diffuse conjunctival neoplasms treated with radioactive phosphorus 32 (32P)-impregnated flexible film. DESIGN, SETTING, AND PARTICIPANTS This retrospective case series between January 1, 2010, and January 1, 2013, was conducted at Memorial Sloan-Kettering Cancer Center, a tertiary referral center. The study was conducted on 7 eyes of 6 patients treated for diffuse conjunctival squamous cell carcinoma, sebaceous carcinoma, or lymphoma that had recurrent or residual disease after primary treatment. INTERVENTIONS Patients underwent mapping biopsies and detailed conjunctival drawings to delineate the pathologic extent of the disease. The brachytherapy film used for treatment was the RIC Conformal Source Model 100 (RIC-100, RI Consultants). The RIC-100 is a flexible, thin (approximately 0.5-mm) film made of a polymer chemically bound to 32P. The radioactive 32P film was placed intraoperatively, allowed to stay in place until the prescription dose was reached, and then removed. The median dose at the prescription point (1 mm from the surface of the film) was 15 Gy (range, 5-17 Gy). MAIN OUTCOMES AND MEASURES Patients were tested for best-corrected visual acuity, recurrence-free survival, and adverse events scored by using the Adult Comorbidity Evaluation-27 scale. RESULTS Between 2010 and 2013, 7 eyes of 6 patients were treated. The median age of patients was 70 years. All patients had a recurrent or persistent neoplasm. Four patients with squamous cell carcinoma, 1 with sebaceous carcinoma, and 1 with metachronous bilateral lymphomas were treated. The median treatment time was 19 minutes (range, 10-52 minutes). The median follow-up was 24.9 months (range, 3.1-38.2 months). Recurrence-free survival 24 months after brachytherapy was 75% (95% CI, 19-89.1). Two moderate adverse events and 1 severe adverse event occurred. Visual acuity was stable or improved in 5 of the 7 eyes (ie, better than 20/70 in the 5 patients who retained their treated eye). CONCLUSIONS AND RELEVANCE Our results show the use of an intraoperative high-dose rate of 32P brachytherapy in selected cases of recalcitrant diffuse conjunctival neoplasms. This technique offers a novel adjunct in the treatment of these cancers. Further follow-up and study are warranted.

32P Brachytherapy Conformal Source Model RIC-100 for High-Dose-Rate Treatment of Superficial Disease: Monte Carlo Calculations, Diode Measurements, and Clinical Implementation

PURPOSE A novel (32)P brachytherapy source has been in use at our institution intraoperatively for temporary radiation therapy of the spinal dura and other localized tumors. We describe the dosimetry and clinical implementation of the source. METHODS AND MATERIALS Dosimetric evaluation for the source was done with a complete set of MCNP5 Monte Carlo calculations preceding clinical implementation. In addition, the depth dose curve and dose rate were measured by use of an electron field diode to verify the Monte Carlo calculations. Calibration procedures using the diode in a custom-designed phantom to provide an absolute dose calibration and to check dose uniformity across the source area for each source before treatment were established. RESULTS Good agreement was established between the Monte Carlo calculations and diode measurements. Quality assurance measurements results are provided for about 100 sources used to date. Clinical source calibrations were usually within 10% of manufacturer specifications. Procedures for safe handling of the source are described. DISCUSSION Clinical considerations for using the source are discussed.

Whole-body clearance kinetics and external dosimetry of 131I-3F8 monoclonal antibody for radioimmunotherapy of neuroblastoma

The purpose of this retrospective study was to evaluate the whole-body clearance kinetics of 131I-3F8 monoclonal antibody, an anti-ganglioside 2 antibody, used in the treatment of pediatric patients with late-stage neuroblastoma (NB). Serial whole-body dose rate measurements were obtained on pediatric patients participating in phase I dose escalation studies of therapeutic 131I-3F8. Whole-body retention fractions were derived and fit for each treatment to exponential curves to determine both the effective half-lives and corresponding clearance fractions. 27 patients were administered 131I-3F8 over the course of cyclical administrations with a median administered activity of 2.5 GBq (range, 1–8.14 GBq), typically every 2–4 d for up to 9 treatment cycles. Based on whole-body dose rate measurements, there was a large variability in the calculated mono-exponential clearance effective half-life time, with a mean of 26.4 h (range, 12.4–45.5 h). The data from a subset of 12 treatments were fit to a bi-exponential curve with a rapid clearance component mean effective half-time of 16.9 h (range, 4.3–26 h) and a slower clearance component mean effective half-time of 65.5 h (range, 16.9–136 h). The use of whole-body dose rate measurements, obtained for patient-release and other radiation safety considerations, can be useful in estimating whole-body clearance kinetics for photon emitting radionuclide labeled mAbs and other therapeutic radiopharmaceuticals. In the case of 131I-3F8 for pediatric NB therapy, the demonstrated variability in effective half-time suggests the need for patient-specific tracer dosimetry for both optimization of treatment and radiation safety precaution decision-making.

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

Although 131I–metaiodobenzylguanidine (131I–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 131I–MIBG using rolling lead shields.

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.

Activity thresholds for patient instruction and release for positron emission tomography radionuclides.

AbstractThe use of unconventional or novel radionuclides for positron emission tomography (PET) is becoming more prevalent in both nuclear medicine diagnosis and therapy. Many of these radionuclides are produced in cyclotrons or are further eluted from generators. Although half-lives from many of these unconventional PET radionuclides are considered relatively short (minutes to hours, but some are days) and the intent of their use is often as a diagnostic imaging agent, patient release criteria and patient radiation safety instruction regulatory requirements are based on estimated dose to a member of the public. This paper reviews a method referenced routinely for patient release criteria as found in U.S. Nuclear Regulatory Commission guidance, estimates fundamental quantities used in the method, compares estimated quantities with the published literature, and calculates release and patient radiation safety instruction criteria for several novel PET radionuclides used in nuclear medicine. It should be recognized that some quantities of novel PET radionuclides in use today reach the threshold for patient safety instruction using conservative model procedures for patient release.