Synthesis of novel peptide nucleic acid-peptide chimera for non-invasive imaging of cancer.
A chelator-peptide-PNA-peptide chimera specific for KRAS has been prepared by continuous solid phase coupling with a C-terminal insulin-like growth factor 1 (IGF1) ligand, D(cys-ser-lys-cys), and N-terminal bis(S-benzoyl thioglycoloyl) diaminopropanoate chelator for radionuclide labeling. The probe was purified by RP-HPLC and characterized by MALDI-TOF mass spectroscopy. The probe was labeled with 99mTc and 64Cu. Both labeled probes accumulated in human pancreatic cancer xenografts in immunocompromised mice. Control experiments with mismatch chimeras and control xenografts will be necessary to determine the specificity of this molecular diagnostic strategy.
Chakrabarti
A
A
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Aruva
M R
MR
Sajankila
S P
SP
Thakur
M L
ML
Wickstrom
Eric
E
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003301:Copper Radioisotopes / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D017434:Protein Structure, Tertiary; D011877:Radionuclide Imaging / Q000295:instrumentation*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013667:Technetium / Q000737:chemistry; D013997:Time Factors
D002614:Chelating Agents; D003301:Copper Radioisotopes; D008024:Ligands; D020135:Peptide Nucleic Acids; D010455:Peptides; D007334:Insulin-Like Growth Factor I; D013667:Technetium