Radiolabeled androgens for imaging and therapy: Radiopharmaceutical investigations and development of animal models

This work expands our efforts with radiolabeled androgens from diagnostic imaging to approach radiotherapy. A fluorinated androgen under evaluation in humans, 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT), was considered the standard. Two other androgens, 16beta-[ 18F]fluoromibolerone (FMib) and 7alpha-iodo-5alpha-dihydrotestosterone (IDHT) were synthesized as well.;A more suitable animal model for evaluating radiolabeled androgens in vivo than the currently used adult male rat model was developed. The major failing of the rat model is lack of sex hormone binding globulin (SHBG), a plasma protein found in many species, including humans, that may positively affect steroid distribution and metabolism. High affinities for SHBG are now desired, necessitating a primary animal model that simulates SHBG's effects. Four models were evaluated: mature rats administered human SHBG, immature rats, immature rabbits and mature rabbits. Both mature and immature rabbits have circulating SHBG, while immature rats have a related protein, androgen binding protein (ABP). A Positron Emission Tomography (PET) imaging protocol for mature rabbits was developed. FDHT and FMib were compared in this model.;To expand the uses of PET and to permit radiotherapy with halogenated steroids, biomedical cyclotron production of I-124, Br-76 and Br-77, via the (p,n) reaction on Te or Se was investigated. In situ target formation was developed to produce CU2Te or CU2Se ready for irradiation. It was shown that these targets were reusable. An enriched (99.8% Te-124) Cu2Te target was made, irradiated, and the I-124 separated to prepare [124I]IDHT to image a rabbit.;Three human ovarian cancer cell lines, OVCAR-3, SKOV-3 and OV-1063, were evaluated as in vivo tumor bearing models in SCID mice using FDHT to determine the feasibility of androgen based imaging and radiotherapy of ovarian cancer. [125I]IDHT was evaluated in both SC and IP OVCAR-3 tumors. Tumors were imaged using PET and FDHT and using electronic autoradiography with both FDHT and [125I]IDHT.;Additional projects were: (1) development of a novel evaporation apparatus using heated nitrogen to accelerate radioisotope processing; (2) examining the reactivity of p-[18F]fluorophenacyl bromide as a radiolabeling agent for proteins and peptides.