title: (44)Sc: an attractive isotope for peptide-based PET imaging.
abstract: The overexpression of integrin αvβ3 has been linked to tumor aggressiveness and metastasis in several cancer types. Because of its high affinity, peptides containing the arginine-glycine-aspartic acid (RGD) motif have been proven valuable vectors for noninvasive imaging of integrin αvβ3 expression and for targeted radionuclide therapy. In this study, we aim to develop a (44)Sc-labeled RGD-based peptide for in vivo positron emission tomography (PET) imaging of integrin αvβ3 expression in a preclinical cancer model. High quality (44)Sc (t1/2, 3.97 h; β(+) branching ratio, 94.3%) was produced inexpensively in a cyclotron, via proton irradiation of natural Ca metal targets, and separated by extraction chromatography. A dimeric cyclic-RGD peptide, (cRGD)2, was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with (44)Sc in high yield (>90%) and specific activity (7.4 MBq/nmol). Serial PET imaging of mice bearing U87MG tumor xenografts showed elevated (44)Sc-DOTA-(cRGD)2 uptake in the tumor tissue of 3.93 ± 1.19, 3.07 ± 1.17, and 3.00 ± 1.25 %ID/g at 0.5, 2, and 4 h postinjection, respectively (n = 3), which were validated by ex vivo biodistribution experiments. The integrin αvβ3 specificity of the tracer was corroborated, both in vitro and in vivo, by competitive cell binding and receptor blocking assays. These results parallel previously reported studies showing similar tumor targeting and pharmacokinetic profiles for dimeric cRGD peptides labeled with (64)Cu or (68)Ga. Our findings, together with the advantageous radionuclidic properties of (44)Sc, capitalize on the relevance of this isotope as an attractive alternative isotope to more established radiometals for small molecule-based PET imaging, and as imaging surrogate of (47)Sc in theranostic applications.
authors: Department of Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors: Reinier
authors: R
authors: Hernandez
authors: Hector F
authors: HF
authors: Valdovinos
authors: Yunan
authors: Y
authors: Yang
authors: Rubel
authors: R
authors: Chakravarty
authors: Hao
authors: H
authors: Hong
authors: Todd E
authors: TE
authors: Barnhart
authors: Weibo
authors: W
authors: Cai
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000737:chemistry; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D012538:Scandium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010455:Peptides; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium; D012538:Scandium