SYNTHESIS, CHARACTERIZATION AND BIODISTRIBUTION OF NEUTRAL AND LIPID-SOLUBLE TC-99M-BISAMINOETHANETHIOL SPIPERONE DERIVATIVES - POSSIBLE LIGANDS FOR RECEPTOR IMAGING WITH SPECT

Using parts of the molecular structure of spiperone, two new ligand sy stems for complexation with [Tc-99m]technetium were prepared in order to develop potential receptor imaging agents for single photon emissio n computer tomography (SPECT). The bis-aminoethanethiols (BAT): yl)-4- (2-mercapto-2-methyl-propylamino)-piperidine (benzylpiperidyl-BAT, BP- BAT) and yl)-4-(2-mercapto-2-methyl-propylamino)-piperidine (butyrophe noylpiperidyl-BAT, BUP-BAT) form stable, neutral and lipid soluble com plexes with [Tc-99m]technetium at pH greater than or equal to 11 using SnCl2 as reducing agent in nearly quantitative radiochemical yields. Biodistribution of Tc-99m-BP-BAT and Tc-99m-BUP-BAT in rats showed a m oderate clearance from blood and low uptake and retention in the liver , whereas brain uptake was moderate, however with prolonged brain rete ntion. On the other hand, significant accumulations and retentions wer e observed in heart, kidney and lung with increasing oxygen/blood rati os up to 24 h. Within 24 h p.i. 22 and 29% of the injected dose (i.d.) of Tc-99m-BP-BAT and Tc-99m-BUP-BAT were eliminated by hepatobiliary excretion whereas 22% i.d, of both Tc-99m-BAT complexes were excreted into the urine. Although first biodistribution studies of Tc-99m-BP-BA T and Tc-99m-BUP-BAT in rats showed relatively low brain uptake, the h igh uptake in peripheral, receptor rich organs indicates that compound s of this type may be used as a basis for further structural modificat ion to develop agents with optimal properties for cerebral or peripher al receptor imaging with SPECT.