Radiohalogenation of biomolecules : An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

Sammanfattning: Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging and inradionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211At and 124I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two.Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap wasdeveloped for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[211At]astato-2´-deoxyuridine (AUdR) and N-succinimidyl-4-[211At]astatobenzoate (SAB) were synthesized in ~95% respectively ~90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(l-) conjugate. The overall labeling yields were ~3.5% for direct labeling, ~44% for SAB and ~70% for the hEGF-nido-carborane conjugate.A new route to N-succinimidyl 3- and 4- [124I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(l-methylpropyl)isoquinoline-3-carboxyamide, a peripheral-type benrodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[124I]iodo-2´-deoxyuridine (IUdR) is presented.The close-dodecaborate anion was evaluated as prosthetic group for radioiodination of macromolecules. Its inertness to in vivo dehalogenation was demonstrated by low thyroidal radioiodine uptake in the rat (0.07% ID/g, 20 h post injection).