188Re- and 99mTc-MAG3 as prosthetic groups for labeling amines and peptides: approaches with pre- and postconjugate labeling

Nucl Med Biol. 1998 Oct;25(7):621-31. doi: 10.1016/s0969-8051(98)00025-0.

Abstract

Either radiolabeled Tc-99m- or Re-188-labeled MAG3-4-nitrophenylester or unlabeled Bz-MAG3-4-nitrophenylester was reacted with amines and peptides to follow a pre- or a postconjugate radiolabeling route, respectively. The model compounds were N'-t-butyloxycarbonyl-1,6-diaminohexane (DH-Boc) and a Lys-protected derivative of the somatostatin analog RC-160 (cyclic D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2). In the case of labeling DH-Boc, both the preconjugate labeling and the postconjugate labeling were found by using analytical HPLC to provide identical 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 188Re- or 99mTc-MAG3-RC-160 somatostatin analog were synthesized following the preconjugate labeling route and subsequent removal of the protecting group. Biodistributions of 188Re-and 99mTc-MAG3-RC-160 were evaluated in normal and tumor-bearing mice, and were similar to those of radioiodinated 131-RC-160. All radiolabeled analogs of RC-160 were rapidly cleared from the blood and were excreted through the hepatobiliary system with very little normal organ uptake. The tumor uptake (PC-3, human prostate adenocarcinoma) of systemically administered Re-188-MAG3-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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemistry*
  • Animals
  • Chromatography, High Pressure Liquid
  • Diamines / chemistry
  • Female
  • Formic Acid Esters / chemistry
  • Mice
  • Mice, Nude
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacokinetics
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacokinetics
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Somatostatin / analogs & derivatives
  • Somatostatin / chemistry
  • Somatostatin / pharmacokinetics
  • Technetium Tc 99m Mertiatide / chemistry*
  • Technetium Tc 99m Mertiatide / pharmacokinetics
  • Time Factors
  • Tissue Distribution

Substances

  • Amines
  • Diamines
  • Formic Acid Esters
  • Oligopeptides
  • Organometallic Compounds
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • rhenium-mercaptoacetyltriglycine
  • t-butyloxycarbonyl group
  • vapreotide
  • Technetium Tc 99m Mertiatide
  • Somatostatin
  • 1,6-diaminohexane