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

99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin-releasing peptide (GRP) receptors. 9 9 m Tc-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 9 9 m Tc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 9 9 m Tc-labeled BN analogue, [DTPA 1 , Lys 3 ( 9 9 m Tc-Pm-DADT), Tyr 4 ]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 9 9 m Tc 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 [DTPA 1 , Lys 3 ( 9 9 Tc-Pm-DADT), Tyr 4 ]BN was 4.1 ′ 1.4 nM. Biodistribution studies of [DTPA 1 , Lys 3 ( 9 9 m Tc-Pm-DADT), Tyr 4 ]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.