Dennis P. Swanson

A multidisciplinary approach to honest broker services for tissue banks and clinical data: a pragmatic and practical model.

Honest broker services are essential for tissue‐ and data‐based research. The honest broker provides a firewall between clinical and research activities. Clinical information is stripped of Health Insurance Portability and Accountability Act‐denoted personal health identifiers. Research material may have linkage codes, precluding the identification of patients to researchers. The honest broker provides data derived from clinical and research sources. These data are for research use only, and there are rules in place that prohibit reidentification. Very rarely, the institutional review board (IRB) may allow recontact and develop a recontact plan with the honest broker. Certain databases are structured to serve a clinical and research function and incorporate ‘real‐time’ updating of information. This complex process needs resolution of a variety of issues regarding the precise role of the HB and their interaction with data. There also is an obvious need for software solutions to make the task of deidentification easier.

Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion.

PURPOSEnHepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution were recently developed, but hepatocyte transplantation systems must be optimized. The authors report their experience with In-111 oxyquinolone labeling of a test dose of hepatocytes (108 cells) for noninvasive assessment of the biodistribution of transplanted hepatocytes in a 5-year-old child with omithine transcarbamoylase deficiency.nnnMATERIALS AND METHODSnDonor hepatocytes (approximately 108) were radiolabeled using a commercially available In-111 oxyquinolone solution (specific activity of 1 mCi/ml).nnnRESULTSnThe overall labeling efficiency was 36.4%. A final dose of approximately 290 ,uCi of the In-111-labeled hepatocytes in 10 ml serum-free phosphate-buffered saline was infused percutaneously into the portal vein approximately 2.5 hours after their preparation. The study was performed 3 hours before cell transplantation (109 cells). Quantitative analysis of the biodistribution of In-111-labeled hepatocytes indicated that cells were predominantly localized in the liver immediately after portal vein-infused transplantation. The predominant hepatic distribution was persistent for as long as 7 days after the procedure, with an average liver-to-spleen ratio of 9.5 to 1. No significant pulmonary radiotracer uptake was present.nnnCONCLUSIONnThese results indicate that In-111 labeling of hepatocytes is useful for the short-term noninvasive analysis of the biodistribution of transplanted hepatocytes.

Radiopaque Contrast Media: The Role of the Pharmacist:

Radiopaque contrast media (ROCM) are diagnostic drugs used for the enhancement of radiographic (x-ray) examinations. Although these agents have been used extensively for several years, pharmacist involvement with this category of drugs, to date, has been minimal. This article outlines several aspects of contrast media use in which pharmacists can or should become actively involved. Included in this discussion are possible roles of the pharmacist in decisions regarding respective product efficacy and use; adverse reaction prevention, reporting, monitoring, and treatment; and the evaluation of potential contrast media-drug or contrast media-laboratory test interactions. Pharmacist involvement associated with the use of traditional drugs in the performance of radiographic examinations and with technological advancements in radiology are also addressed. The overall magnitude of drug activity encountered in a radiology department suggests a needed and important role for pharmacists interested in this area.

Research involving the newly dead: an institutional response.

I nvestigators at a university hospital, having completed testing on several types of large animals, want to test a new device on humans. Because this is a new technology, they want to minimize risk to humans. Therefore, they decide to perform the research on brain-dead individuals who are ineligible for organ donation. They submit the project to the institutional review board (IRB), which declares that the project does not fall under their purview. The investigators, wanting administrative approval for the study, present the situation to the hospital’s ethics committee.

The Future of USP Monographs for PET Drugs

1Washington University School of Medicine, St. Louis, Missouri; 2Committee on Pharmacopeia, Society of Nuclear Medicine and Molecular Imaging, Reston, Virginia; 3University of New Mexico Health Sciences Center, Albuquerque, New Mexico; 43D Imaging, LLC, University of Arkansas for Medical Sciences, Little Rock, Arkansas; 5Beth Israel Deaconess Medical Center, Boston, Massachusetts; 6Mayo Clinic, Rochester, Minnesota; 7University of Washington, Seattle, Washington; 8Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsyvania; 9Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts; 10Brigham and Women’s Hospital, Boston, Massachusetts; 11Duke University Medical Center, Durham, North Carolina; 12University of Iowa, Iowa City, Iowa; 13Seifert and Associates, Los Angeles, California; 14University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania; 15Ron Weiner Services, Sherman Oaks, California; and 16Siemens PETNET Solutions, Knoxville, Tennessee

Prospective randomized trial of hepatic artery chemotherapy with cisplatin and doxorubicin, with or without lipiodol in the treatment of advanced stage hepatocellular carcinoma.

Purpose This randomized study assessed the responses in hepatocellular carcinoma (HCC) to hepatic arterial doxorubicin plus cisplatin, with or without lipiodol. Patients and Methods Patients with unresectable and biopsy-proven HCC were treated with doxorubicin (30 mg/m2) plus cisplatin (100 mg/m2) without (Solution) or with (Lipiodol) emulsification every 2 months till tumor progression. Primary end point was response. Results Partial response rate was 56.8% for Lipiodol and 47% for Solution, P=0.48. Responses were evaluated as tumor size changes without vascularity assessments, due to the lipiodol. There were no complete responses. Survival at 6,12,18, and 24 months was 65, 32, 27, and 10.8% for Lipiodol patients and 70.6, 26.6, 8.8, and 8.8 for Solution patients. Of the total 71 enrolled and evaluable patients, survival at 6, 12, and 18 months was 75.7, 40, and 35% for responders and 58.8, 17.6, and 0 for nonresponders. There were no clear clinical or biochemical profile differences between the 2 treatment groups or between responders and nonresponders. Conclusions Lipiodol conferred a minor response advantage, recorded as tumor size change, to hepatic arterial chemotherapy with doxorubicin plus cisplatin for HCC, but no survival advantage.

Radiopharmaceuticals as orphan drugs

Rare diseases and conditions are defined as diseases or conditions that affect less than 200,000 individuals in the United States. Because of the limited population suffering from any given rare disorder, there is little economic motivation for the development of drug products for its diagnosis or treatment. Also, frequently these rare diseases are misdiagnosed or undiagnosed due to a lack of familiarity with their symptoms and course. Thus, these rare disorders are commonly referred to as orphan diseases or conditions. To address this problem, legislation has been enacted that provides for incentives for the development of drug products for rare diseases or conditions (i.e., orphan drug products). Nuclear medicine scientists can take advantage of these incentives in the development of orphan radiopharmaceuticals for the treatment or diagnosis of rare diseases or conditions. Nuclear medicine physicians should know where information on orphan diseases and orphan radiopharmaceuticals can be obtained to maximize the care of their patients.

Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: Interim results of a phase I trial

AbstractBackground: Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensity therapy without associated toxicity.nMethods: The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC.nResults: In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients.nConclusions: This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.

Explanations and Unresolved Issues Pertaining to the Development of the Nuclear Pharmacy Compounding Guidelines

OBJECTIVESnTo provide background information related to the development of the Nuclear Pharmacy Compounding Guidelines, to discuss regulatory complexities related to radiopharmaceutical compounding practice, and to summarize the gaps in the current compounding regulations for radiopharmaceuticals.nnnDATA SOURCESnThe Guidelines closely follow the provisions of section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the monographs and chapters related to pharmacy compounding in the United States Pharmacopeia (USP), and the recommended guidelines published by the American Society of Health-System Pharmacists.nnnSUMMARYnThe Food and Drug Administration Modernization Act (FDAMA) of 1997 established parameters under which the compounding of drug products is appropriate and lawful, but these criteria expressly do not apply to radiopharmaceuticals. The Nuclear Pharmacy Compounding Practice Committee, a group of nuclear pharmacists convened by the American Pharmaceutical Association, developed the Nuclear Pharmacy Compounding Guidelines to establish a set of principles and guidelines for good radiopharmaceutical compounding practice. The intent of the new document is to provide guidance on radiopharmaceutical compounding practices that have evolved over the last 2 decades and to place them in an appropriate regulatory framework in accordance with previous enforcement policies and guidelines issued by the U.S. Food and Drug Administration (FDA) regarding the exemption of certain pharmacy practices from enforcement of adulteration, misbranding, and new drug requirements.nnnCONCLUSIONnThe Nuclear Pharmacy Compounding Guidelines, recently released by APhA, is the first official document that provides realistic and practical compounding guidance for nuclear pharmacists. Even though the United States Court of Appeals for the Ninth Circuit recently ruled section 503A of the FD&C Act to be invalid in its entirety, and the Supreme Court upheld that ruling, the compliance policy guides issued by FDA in March 1992 and revised in May 2002 maintain guiding principles on pharmacy compounding similar to those stated in section 503A of the FD&C Act. The Nuclear Pharmacy Compounding Practice Committee is optimistic that the practical information contained in the Guidelines will assist state boards of pharmacy, FDA, and the United States Pharmacopeial Convention in setting appropriate standards for nuclear pharmacy compounding practice that will ensure the continued availability of high-quality compounded radiopharmaceuticals at reasonable cost.

Pharmacy Practice and Positron Emission Tomography

Positron emission tomography (PET) is an imaging technique that has recently experienced growth because of its unique advantages (1). Unlike computerized axial tomography (CAT) or magnetic resonance imaging (MRI), which visualize anatomical structure, PET permits noninvasive assessment of human physiology and organ function. PET data is derived from the tissue accumulation of tracer, which is intrinsically related to the biochemical and metabolic processes that affect the radiopharmaceutical in vivo.