Synthesis and biodistribution of Tc-99m bis-aminoethanethiol (BAT) complexes with amine side chains
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-; TRN: 87-010626
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
AMINES
CHEMICAL PREPARATION
BRAIN
METABOLISM
RADIOPHARMACEUTICALS
RETENTION FUNCTIONS
TISSUE DISTRIBUTION
UPTAKE
TECHNETIUM COMPLEXES
AUTORADIOGRAPHY
INTRAVENOUS INJECTION
LABELLING
MONKEYS
RADIOCHEMISTRY
RADIONUCLIDE KINETICS
TECHNETIUM 99
WASHOUT
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
CHEMISTRY
COMPLEXES
DISTRIBUTION
DRUGS
FUNCTIONS
HOURS LIVING RADIOISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRECIPITATION SCAVENGING
PRIMATES
RADIOISOTOPES
SEPARATION PROCESSES
SYNTHESIS
TECHNETIUM ISOTOPES
TRANSITION ELEMENT COMPLEXES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550101 - Behavioral Biology- Tracer Techniques
400201 - Chemical & Physicochemical Properties