Comprehensive Cancer Center (CCC) Radiolabeling/Imaging/Dosimetry Shared Facility (RIDSF) Director: Ahmad Safavy, PhD Department/Center Association: CCC Established: 1994 Mission The Radiolabeling/Imaging/Dosimetry Shared Facility (RIDSF) was established to provide radiolabeling services for in vitro laboratory studies, in vivo animal model investigations, and in vivo human clinical protocols. The facility has extensive experience with radiolabeling procedures for a wide range of radioactive isotopes and provides appropriate quality control procedures to assure standardized and high-quality reagents to Comprehensive Cancer Center (CCC) members. The primary objective of the RIDSF is to provide high-quality radiolabeled reagents for in vitro studies and for in vivo use in animals and humans. Research Information The RIDSF has been a major component of the CCC’s research effort in targeted immunotherapy. It has provided research faculty from Tumor Immunology, Experimental Therapeutics, Women’s Cancer, and more recently, Neuro-Oncology with quality radiolabeled reagents for pre-clinical and clinical investigations. It has had experience with radiolabeling antibodies, fusion proteins, peptides, and other molecules using a wide range of radioisotopes. It also has one of the largest experiences in the world with preparation of human use radiolabeled reagents for clinical trials, which have utilized 125I, 131I, 90Y, 111In, 172Lu, 186Re and 188 Re. These studies have progressed from radiolabeled murine monoclonal antibodies, to genetically engineered humanized reagents and more recently the use of novel fusion proteins in pretargeting format. The facility has supported more than 25 clinical trials resulting in over 45 publications and an equal number of publications on preclinical studies. The presence of this high-quality radiolabeling facility and research gamma camera has been a major factor in allowing our Cancer Center to take the lead in developing new radioimmunotherapy paradigms over the current funding period including: Use of a genetically engineered humanized antibody (CC49) with a deleted CH2 region to provide a novel targeting molecule with low immunogenicity and short plasma half-life. These studies include 131I-CC49∆CH2 I.V. for GI malignancies and I.P. in ovarian cancer as well as a conjugated form of the molecule for IIIIn/90Y trials. Use of a novel fusion protein composed of four single chain antibodies and the four chains of streptavidin as the targeting moiety in pretargeting radioimmunotherapy. We have completed initial phase-I trials in lymphoma (anti CD20) and GI cancer (anti TAG72) and await reagents for further phase I/II trials. Use of a novel 131I-labeled chlorotoxin (peptide) for intracavitary delivery in resected recurrent glioblastoma multiforme. In addition, we participated in the development of Zevalin (FDA approval for follicular lymphoma) and are currently supporting UAB-led trials to optimize its use. Thus, the facility is vitally important to one of the major translational research efforts of the Cancer Center with involvement of faculty from multiple programs and SPORES. Services and Fees The facility generates radiolabeled reagents for human use including safety-oriented procedures for large doses of therapeutic radioactive investigational agents. The expansion of the facility’s capabilities, including the purchase of an AXIS (Picker International/Marconi) dualhead camera imaging system in 2001, provides high quality imaging and dosimetry estimate analysis for the protocols in our immunotherapy program. The development of these additional capabilities has allowed the facility to play an important role in our translational research and targeted immunotherapy efforts. The facility provides consultation services related to radiolabeling of proteins, peptides, and oligonucleotides, to CCC members. In addition, it provides a centralized purchasing of isotopes, which leads to a very cost-effective utilization of research funds for CCC members. The facility also has responsibility for radiation waste management in the Wallace Tumor Institute including acquisition, utilization, and documentation of waste generation and disposal. It provides documentation of all radiolabeled reagents for human use according to FDA, state, and other regulatory agencies. The RIDSF is the CCC’s interface with the Radiation Safety Department and Waste Management group of UAB. Specific services provided by this shared facility include: Radiolabeled reagents for in vitro studies, which have rigorous quality control regarding degree of isotope binding and reactivity. Radiolabeled reagents for in vivo animal experimentation, which have appropriate analysis for purity, specificity, and structural integrity. Radiolabeled reagents for in vivo human use, which fulfill guidelines of the UAB Radioisotope Committee and the FDA. Consultation to CCC investigators regarding radiolabeling technology and custommade radiolabeling procedures to meet the needs of Center investigators. Coordination the radioactive waste management in the Wallace Tumor Institute in regard to interface with the Radiation Safety Department and Waste Management. Provision of high quality imaging and dosimetry estimate analysis for clinical trials of radioimmunotherapy. Contact Information Director: Ahmad Safavy, PhD Email: safavy@uab.edu Phone: 205-934-3681 Web site: http://www3.ccc.uab.edu/show.asp?durki=59564 Approved by: Ahmad Safavy, PhD, Director Date: February 6, 2007