99mTc labeled VIP analog:: evaluation for imaging colorectal cancer

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with Tc-99m, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of Tc-99m-TP3654 has been compared with that of In-111-DTPA-Octreotide and Tc-99m-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of Tc-99m-TP3654 have been performed in four normal human volunteers. Data suggest that Tc-99m-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of Tc-99m-TP3654 in the animal model used was modest (0.21 +/- 0.07% I.D./g), the tissue distribution profile was more favorable than that of In-111-DTPA-Octreotide or Tc-99m-anti-CEA scan. Human studies indicated that Tc-99m-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting Volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that Tc-99m-TP3654 is a promising agent for imaging colorectal cancer. (C) 2001 Elsevier Science Inc. All rights reserved.