Many tumors such as glioblastoma, small cell lung cancer, prostate, breast, gastric, and colon cancer are known to over express receptors to bombesin/gastrin releasing peptide (GRP). Evidence is accumulating in many cases studied that receptors to bombesiin/GRP are present in transformed cells as well as advanced cancer cells but not on surrounding normal tissue. Radiolabeled bombesin/GRP analogues, therefore, have the potential for use in early detection of cancer as well as the selection of patients who could benefit from therapeutic regimens based on bombesin/GRP receptor antagonism. Since the binding of bombesin/GRP agonists to the bombesirdGRP receptor leads to internalization of the agonist-receptor complex, it is conceivable that the labeling of bombesin/GRP receptor agonists with cytotoxic radionuclides, such as 188Re would lead to analogues having radiotherapeutic utility for bombesin receptor-positive cancer. Therefore, our goal is to develop high affinity 99mTc- and 188Relabeled bombesin/GRP analogues that can be used for the in vivo biochemical characterization and radiotherapy of bombesirdGRP receptor-positive cancer. To solve the problem of high hepatobiliary clearance that generally plagues Tc and Re labeled peptides, our design of the Tc, and Re labeled bombesin/GRP analogues incorporate a pharmacokinetic modifier to direct clearance through the urinary system rather than the hepatobiliary system. The leading analogues developed by this concept show great specificity and high target to non-target differentiation while exhibiting low hepatobiliary uptake. The tracers proposed in this project have great potential for applications in many cancers.
| Lin, Kuo-Shyan; Luu, Andrew; Baidoo, Kwamena E et al. (2005) A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation. Bioconjug Chem 16:43-50 |
| Lin, Kuo-Shyan; Luu, Andrew; Baidoo, Kwamena E et al. (2004) A new high affinity technetium analogue of bombesin containing DTPA as a pharmacokinetic modifier. Bioconjug Chem 15:1416-23 |
