title: Synthesis and investigation of a radioiodinated F3 peptide analog as a SPECT tumor imaging radioligand.
abstract: A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[(125)I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [(125)I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C(5) maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C(2) maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [(125)I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [(125)I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [(125)I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Mahaveer S
authors.initials: MS
authors.lastname: Bhojani
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ranga
authors.forename: Gary D
authors.initials: GD
authors.lastname: Luker
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.forename: Marcian E
authors.initials: ME
authors.lastname: Van Dort
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D005456:Fluorescent Dyes; C568272:IBMF3 peptide; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008024:Ligands; D010455:Peptides; D019275:Radiopharmaceuticals