title: 188Re- and 99mTc-MAG3 as prosthetic groups for labeling amines and peptides: approaches with pre- and postconjugate labeling.
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).
authors.affiliation: Klinik Für Nuklearmedizin, University of Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Guhlke
authors.forename: A
authors.initials: A
authors.lastname: Schaffland
authors.forename: P O
authors.initials: PO
authors.lastname: Zamora
authors.forename: J
authors.initials: J
authors.lastname: Sartor
authors.forename: D
authors.initials: D
authors.lastname: Diekmann
authors.forename: H
authors.initials: H
authors.lastname: Bender
authors.forename: F F
authors.initials: FF
authors.lastname: Knapp
authors.forename: H J
authors.initials: HJ
authors.lastname: Biersack
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003959:Diamines / Q000737:chemistry; D005260:Female; D005563:Formic Acid Esters / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D017263:Technetium Tc 99m Mertiatide / Q000737:chemistry* / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000588:Amines; D003959:Diamines; D005563:Formic Acid Esters; D009842:Oligopeptides; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C114893:rhenium-mercaptoacetyltriglycine; C000345:t-butyloxycarbonyl group; C051458:vapreotide; D017263:Technetium Tc 99m Mertiatide; D013004:Somatostatin; C007297:1,6-diaminohexane