title: 99mTc labeled VIP analog: evaluation for imaging colorectal cancer.
abstract: 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 (99m)Tc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of (99m)Tc-TP3654 has been compared with that of (111)In-DTPA-Octreotide and (99m)Tc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of (99m)Tc-TP3654 have been performed in four normal human volunteers. Data suggest that (99m)Tc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of (99m)Tc-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 (111)In-DTPA-Octreotide or (99m)Tc-anti-CEA scan. Human studies indicated that (99m)Tc-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 (99m)Tc-TP3654 is a promising agent for imaging colorectal cancer.
authors.affiliation: Thomas Jefferson University, Department of Radiology, Philadelphia, PA, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Rao
authors.forename: M L
authors.initials: ML
authors.lastname: Thakur
authors.forename: V
authors.initials: V
authors.lastname: Pallela
authors.forename: R
authors.initials: R
authors.lastname: Patti
authors.forename: K
authors.initials: K
authors.lastname: Reddy
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: H L
authors.initials: HL
authors.lastname: Pham
authors.forename: L
authors.initials: L
authors.lastname: Diggles
authors.forename: C
authors.initials: C
authors.lastname: Minami
authors.forename: C S
authors.initials: CS
authors.lastname: Marcus
mesh_terms: D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging*; D006801:Humans; D007205:Indium Radioisotopes; D007668:Kidney / Q000378:metabolism; D015282:Octreotide / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000378:metabolism; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D007205:Indium Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D018005:Receptors, Vasoactive Intestinal Peptide; C117473:TP 3654; D014660:Vasoactive Intestinal Peptide; D013667:Technetium; D015282:Octreotide