title: Development of a new positron emission tomography tracer for targeting tumor angiogenesis: synthesis, small animal imaging, and radiation dosimetry.
abstract: Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET). To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c.) Lewis lung carcinoma (LLC) mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.
authors.affiliation: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA. cam_patterson@med.unc.edu
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.forename: C Brandon
authors.initials: CB
authors.lastname: Frederick
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dyer
authors.forename: Pamela
authors.initials: P
authors.lastname: Lockyer
authors.forename: David S
authors.initials: DS
authors.lastname: Lalush
authors.forename: Anka N
authors.initials: AN
authors.lastname: Veleva
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D003300:Copper / Q000737:chemistry; D005260:Female; D007554:Isotopes / Q000737:chemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007554:Isotopes; D010455:Peptides; D019275:Radiopharmaceuticals; D003300:Copper