Synthesis and biodistribution of Tc-99m bis-aminoethanethiol (BAT) complexes with amine side chains

Conference · Wed May 01 04:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:6856498

Kung, H F; Efange, S; Yu, C C; Billings, J; Blau, M

In order to prepare BAT derivatives with secondary and tertiary monoamine and diamine side chains, a new synthetic route was developed. The activated ester of t-BOC protected 2,3-diaminopropionic acid was condensed with amines. Following the deprotection, the diamine was reacted with 2,2'-dithio-bis-(2-methylpropoanal), the diimine was subsequently reduced to form the BAT ligand. Based on this reaction scheme, compound 1, a monoamine and compound 2, a diamine, were prepared. After labeling with Tc-99m, biodistribution of the two amines was studied in rats. The Tc-99m 1 showed high lipid solubility and high initial (2 min.) brain uptake, 3.8% dose/organ. At 15 min. after the iv injection, the brain retention was still significant, 0.9% dose/organ. On the other hand Tc-99m 2 showed low partition coefficient (P.C.) and low but persistent brain uptake. Protein binding, i.e., 30% and 40% free for Tc-99m 1 and 2, respectively, seems to have little effect on the brain uptake and retention. An imaging study of a monkey after an i.v. injection of Tc-99m 1 indicated that the compound did localize in brain with T/sub 1/2/ for washout = 42 min. More importantly, autoradiograms of Tc-99m 1 at 2 min. and 15 min. showed retention in the brain with more or less fixed regional distribution. The Tc-99m 1 may not be ideal as a brain perfusion imaging agent, nonetheless, it demonstrated the feasibility of increasing the brain uptake and retention by adding an amine group to a neutral Tc-99m complex.

• Research Organization: Dept. of Nuclear Medicine, SUNY/Buffalo, NY
• OSTI ID: 6856498
• Report Number(s): CONF-850611-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 26:5
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400201 -- Chemical & Physicochemical Properties
550101 -- Behavioral Biology-- Tracer Techniques
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
CHEMISTRY
COMPLEXES
DISTRIBUTION
DRUGS
FUNCTIONS
HOURS LIVING RADIOISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LABELLING
MAMMALS
METABOLISM
MONKEYS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRECIPITATION SCAVENGING
PRIMATES
RADIOCHEMISTRY
RADIOISOTOPES
RADIONUCLIDE KINETICS
RADIOPHARMACEUTICALS
RETENTION FUNCTIONS
SEPARATION PROCESSES
SYNTHESIS
TECHNETIUM 99
TECHNETIUM COMPLEXES
TECHNETIUM ISOTOPES
TISSUE DISTRIBUTION
TRANSITION ELEMENT COMPLEXES
UPTAKE
VERTEBRATES
WASHOUT
YEARS LIVING RADIOISOTOPES