New brain perfusion imaging agents based on /sup 99m/Tc-bis(aminoethanethiol) complexes: stereoisomers and biodistribution

Journal Article · Wed Feb 01 00:00:00 EST 1989 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00122a024· OSTI ID:6325434

Kung, H F; Guo, Y Z; Yu, C C; Billings, J; Subramanyam, V; Calabrese, J C

In developing new brain perfusion imaging agents, we prepared /sup 99m/Tc complexes of racemic mixtures of bis(aminoethanethiol) (BAT) derivatives containing an N'-benzylpiperazinyl (BPA) side chain. Due to the presence of a chiral center, a mixture of diastereomers (syn and anti) following chelation with the /sup 99m/Tc (no-carrier-added) was obtained. The neutral and lipid-soluble /sup 99m/Tc-BPA-BAT (/sup 99m/Tc, T1/2 = 6 h) isomers were separated. The syn and anti isomers of carrier-added 99Tc-BPA-BAT (99Tc, T1/2 = 2 x 10(5) years) were also synthesized, separated, and crystallized. The X-ray crystallography of 99Tc-BPA-BAT showed the syn and anti conformations (in relationship with the central TC(=O)N2S2 core). Despite a similarity in the partition coefficients for the two isomers, the syn isomer showed a higher in vivo brain uptake and longer brain retention in rats (2.77 and 1.08% dose/organ at 2 and 15 min) than that of the corresponding anti isomer (0.57 and 0.27% dose/organ at 2 and 15 min). This information is important and should be taken into consideration when new /sup 99m/Tc-labeled brain perfusion imaging agents are being designed.

• Research Organization: SUNY, Buffalo (USA)
• OSTI ID: 6325434
• Journal Information: J. Med. Chem.; (United States), Vol. 32:2
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
RADIOPHARMACEUTICALS
TISSUE DISTRIBUTION
BRAIN
CHEMICAL PREPARATION
COMPLEXES
ISOMERIC NUCLEI
ISOMERS
LIGANDS
PERFUSED ORGANS
PIPERAZINES
RATS
TECHNETIUM 99
TRACER TECHNIQUES
X-RAY DIFFRACTION
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
COHERENT SCATTERING
DIFFRACTION
DISTRIBUTION
DRUGS
HETEROCYCLIC COMPOUNDS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRAZINES
RADIOISOTOPES
RODENTS
SCATTERING
SYNTHESIS
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550601* - Medicine- Unsealed Radionuclides in Diagnostics