THE SYNTHESIS OF RADIOPHARMACEUTICALS LABELED WITH SHORT-LIVED ISOTOPES.

摘要

Short-lived positron-emitting isotopes are of recent interest as labels for radiopharmaceuticals. This is due both to the dosimetry advantages to the patient and to the development of positron emission tomography. Fluorine-18 and carbon-11 are potentially very useful isotopes of this class. Their half-lives of 110 and 20 minutes allow a reasonable time for manipulation while their chemical properties make them potential tracers for virtually any biologically interesting molecule. It remains for chemists to develop the methods for achieving that potential.;In this paper various aspects of the design and synthesis of radiopharmaceuticals are discussed as they relate to the use of short-lived isotopes. Special attention is given to the positron-emitting isotopes and their particular advantages and disadvantages.;The synthesis of two classes of labeled molecules, fluorine-18 labeled fluoropalmitic acids and carbon-11 labeled N-methylenkephalins, have been developed and are reported. The physiological considerations necessary for choosing an appropriate radiopharmaceutical, design of the synthesis, synthetic procedure development and product identification and handling are explored in each case.;Fluorine-18 labeled fluoropalmitic acid was found to be easily prepared in two hours from a precursor whose synthesis is reported. Studies of the in vivo uptake characteristics of fluoropalmitate in various tissues were performed in rats. The radiopharmaceutical was found to have in vivo uptake in the myocardium equal to, and in some aspects better than, the currently used carbon-11 labeled palmitic acid. Uptake was observed primarily in the heart and liver and, at longer times, in the bone.;A general method for the labeling of proteins with carbon-11 was explored in the course of the labeling of methionine enkephalin. Carbon-11 formaldehyde was used to N-methylate enkephalin by reductive amination with sodium borohydride. Radiochemical yields of 50% based on labeled formaldehyde were obtained. The products of the reaction were rigorously characterized. The dependance of the labeling yield of the procedure on the concentration of protein in solution was also explored. The procedure resulted in N-methyl-methionine enkephalin labeled in the N-methyl position with carbon-11.