RE-188-MAG(3) AND TC-99M-MAG(3) AS PROSTHETIC GROUPS FOR LABELING AMINES AND PEPTIDES - APPROACHES WITH PRECONJUGATE AND POSTCONJUGATE LABELING

Either radiolabeled Tc-99m or Re-188-labeled MAG(3)-4 -nitrophenyleste r or unlabeled Bz-MAG(3)-4-nitrophenylester was reacted with amines an d peptides to follow a pre- or a postconjugate radiolabeling route, re spectively. The model compounds were N'-t-butyloxycarbonyl-1,6-diamino hexane (DH-Boc) and a Lys-protected derivative of the somatostatin ana log RC-160 (cyclic D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2). In the ca se of labeling DH-Boc, both the preconjugate labeling and the postconj ugate labeling were found by using analytical HPLC to provide identica l radiolabeled compounds regardless whether Re-188 or Tc-99m was used. The results are supported by infrared and mass-spectral data obtained from compounds synthesized using stable rhenium, The Re-188- or Tc-99 m-MAG(3)-RC-160 somatostatin analog were synthesized following the pre conjugate labeling route and subsequent removal of the protecting grou p. Biodistributions of Re-188, and Tc-99m-MAG(3)-RC-160 were evaluated in normal and tumor bearing mice, and were similar to those of radioi odinated I-131-RC-160. All radiolabeled analogs of RC-160 were rapidly cleared from the blood and were excreted through the hepatobiliary sy stem with very little normal organ uptake. The tumor uptake (PC-3, hum an prostate adenocarcinoma) of systemically administered Re-188-MAG(3) -RC160 was very low, and it reached only 0.28% injected dose/g (%IDg) at 24 h postinjection, similar to what was obtained with I-131-RC-160. Intratumor injections resulted in significant tumor retentions (9.3% ID/g at 24 h), NUCL (C) 1998 Elsevier Science Inc.