Synthesis of radiopharmaceuticals labeled with short-lived isotopes

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1980

OSTI ID:5432107

Berridge, M S

Short-lived positron-emitting isotopes are of recent interest as labels for radiopharmaceuticals. Fluorine-18 and carbon-11 are potentially very useful isotopes of this class. In this paper various aspects of the design and synthesis of radiopharmaceuticals are discussed as they relate to the use of short-lived isotopes. 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 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 dependence 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.

• OSTI ID: 5432107
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702 -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
560172 -- Radiation Effects-- Nuclide Kinetics & Toxicology-- Animals-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BONE CELLS
CARBON 11
CARBON ISOTOPES
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CONNECTIVE TISSUE CELLS
DESIGN
DIGESTIVE SYSTEM
DRUGS
EVEN-ODD NUCLEI
FLUORINE 18
FLUORINE ISOTOPES
GLANDS
HEART
HEXADECANOIC ACID
HOURS LIVING RADIOISOTOPES
IN VIVO
ISOTOPES
LABELLED COMPOUNDS
LABELLING
LIGHT NUCLEI
LIPOTROPIC FACTORS
LIVER
MAMMALS
METHIONINE
MINUTES LIVING RADIOISOTOPES
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
RADIONUCLIDE KINETICS
RADIOPHARMACEUTICALS
RATS
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES