A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation

Kuo Shyan Lin, Andrew Luu, Kwamena E. Baidoo, Hossein Hashemzadeh-Gargari, Ming Kai Chen, Kenneth Brenneman, Roberto Pili, Martin Pomper, Michael A. Carducci, Henry N. Wagner

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin- releasing peptide (GRP) receptors. 99mTc-labeled peptides, however, have a tendency to accumulate in the liver and intestines due to hepatobiliary clearance as a result of the lipophilicity of the 99mTc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 99mTc-labeled BN analogue, [DTPA1, Lys3(99mTc-Pm-DADT), Tyr 4]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 99mTc using a hydrophilic diaminedithiol chelator (Pm-DADT) to effect low hepatobiliary clearance. In vitro binding studies using human prostate cancer PC-3 cell membranes showed that the inhibition constant (K i) for [DTPA1, Lys3(99Tc-Pm-DADT), Tyr4]BN was 4.1 ± 1.4 nM. Biodistribution studies of [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN in normal mice showed very low accumulation of radioactivity in the liver and intestines (1.32 ± 0.13 and 4.58 ± 0.50% ID, 4 h postinjection, respectively). There was significant uptake (7.71 ± 1.37% ID/g, 1 h postinjection) in the pancreas which expresses BN/GRP receptors. The uptake in the pancreas could be blocked by BN, partially blocked by neuromedin B, but not affected by somatostatin, indicating that the in vivo binding was BN/GRP receptor specific. Scintigraphic images showed specific, high contrast delineation of prostate cancer PC-3 xenografts in SCID mice. Thus, the new peptide has a great potential for imaging BN/GRP receptor-positive cancers located even in the abdomen.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalBioconjugate Chemistry
Issue number1
StatePublished - 2005

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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