SNMMI Clinical Trial Network Research Series for Technologists: Application of Good Clinical Practice to Clinical Research in Medical Imaging.

This article is part of a series developed by the Clinical Trials Network of the Society of Nuclear Medicine and Molecular Imaging to offer training and information for molecular imaging technologists and researchers about various aspects of clinical research. This article covers the topic of good clinical practice and how that relates to those portions of the Code of Federal Regulations that govern clinical research in the United States, such as title 21, part 312, and the Common Rule. The purpose of this article is to inform technologists and researchers about standard roles, documents, guidance, and processes that are elemental to the conduct of clinical trials and to offer additional resources for learning about these processes.

Technical Considerations in Brain Amyloid PET Imaging with 18F-Florbetapir.

Technical factors play a critical role in the production of best-quality amyloid PET images for interpretation. This article provides specific instructions and general technical information about PET brain scanning of ß-amyloid neuritic plaques. The focus of tracer-specific information will be on (18)F-florbetapir (indications, contraindications, dosing, administration, uptake time, scanning time, acquisition, processing, biodistribution, radiation dose, adverse events, and display). General scanning information relevant to all amyloid-imaging agents will be also be presented (e.g., mechanism of uptake, safe handling, positioning, prevention of patient motion, processing, and artifacts).

A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

INTRODUCTION: (131)I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of (131)I-CLR1404. METHODS: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131)I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127)I-CLR1404 mass measurements. To evaluate renal clearance of (131)I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software. RESULTS: Single administrations of 370 MBq of (131)I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127)I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. CONCLUSIONS: Preliminary data suggest that (131)I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT00925275.

The importance of standard operating procedures in clinical trials.

This special contribution provides insight into the role that standard operating procedures (SOPs) play in an imaging department and their value in building a high-quality research site. If you have ever participated in a clinical trial, many of the principles described in this article should be familiar. However, this article goes a step further by presenting information from a pharmaceutical or device sponsor's point of view-what the sponsor expects from a site during the course of a research study. This article is intended not to provide a complete set of instructions on how to create a great SOP but, instead, to present guidelines to ensure that the key elements are included. After reading the article, you will be able to define SOPs as they pertain to the clinical trial environment, describe key components of an SOP, list the clinical research SOPs that exist in your institution and imaging department, identify which additional SOPs might improve site performance, and describe how the sponsor relies on SOPs to ensure that the highest quality of research is attained.

Clinical trials in molecular imaging: the importance of following the protocol.

Nuclear medicine technologists and investigators who perform imaging procedures in clinical trials often have not received training on clinical research regulations, such as Title 21, part 312, of the Code of Federal Regulations or Good Clinical Practices. These regulations directly affect implementation of the therapeutic or imaging protocol. Lack of understanding of the regulatory expectations in clinical research can lead to unintended errors or omissions in critical data that are needed for development of a new drug. One common error is not following the protocol exactly as written, or modifying the imaging parameters in some way as to make the data nonstandard from site to site. These errors and omissions are a source of delay in the development of new imaging and therapeutic products. Although not following the protocol does not result in criminal penalties per se, errors and omissions can lead to regulatory consequences such as warning letters to the investigator or sponsor, which if not resolved can lead to barring a site or investigator from participation in any future research trials. Pharmaceutical sponsors, device sponsors, and federal granting agencies such as the National Cancer Institute enter into contracts with imaging sites under the expectation that the investigator and all research staff know and understand clinical research regulations. This article is intended to teach imaging personnel what any sponsor (pharmaceutical, device, or federal agency) is expecting from research imaging and how lack of understanding of Good Clinical Practices and federal regulations can impede the optimal success of a research study. After reading this article, nuclear medicine technologists should be able to understand the importance of following the clinical trial protocol to exact specifications, create a list of questions that should be answered by the sponsor or trial organizers before patient enrollment, describe Form FDA 1572, and describe the terms protocol, protocol deviation, protocol violation, and protocol exception.