Novel 99mTc-labeled neurotensin analogues with optimized biodistribution properties.
Two new 99mTc-labeled neurotensin(8-13) analogues containing the retro-N(alpha)-carboxymethyl-histidine ((N(alpha)His)Ac) chelator were synthesized as potential radiopharmaceuticals for visualization of pancreatic carcinoma. To improve the pharmacokinetic properties, (N(alpha)His)Ac-Arg-NMeArg-Pro-Tyr-Tle-Leu (NT-XII), which is metabolically stabilized at two positions, was further modified. Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) was introduced to obtain a more hydrophilic peptide (NT-XVIII), or Tyr11 was replaced by 2,6-dimethyltyrosine (Dmt) resulting in a triple-stabilized NT(8-13) analogue (NT-XIX). The latter has the best biodistribution profile.
Maes
Veronique
V
Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
Garcia-Garayoa
Elisa
E
Bläuenstein
Peter
P
Tourwé
Dirk
D
D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009496:Neurotensin / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010949:Plasma; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012765:Shikimic Acid / Q000737:chemistry; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
C509710:(99mTc(CO)(3))-(NalphaHis)acetyl-arginyl-N-methylarginyl-prolyl-2',6'-dimethyltyrosyl-alpha-tert-butylglycyl-leucine; D002614:Chelating Agents; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D012765:Shikimic Acid; D009496:Neurotensin; C054381:neurotensin (8-13)