Keywords: 111in, Cholecystokinin Receptors, Neuroendocrine Tumors, Peptides, Preclinical Studies, Cholecystokinin Octapeptide, Indium 111, Pentetate Indium In 111, Pentetic Acid, Cholecystokinin B Receptor, Diagnostic Agent, Drug Derivative, Indium Dtpa Glu G Cck8, Indium Dtpa-Glu-G-Cck8, Radiopharmaceutical Agent, Amino Terminal Sequence, Animal Experiment, Animal Model, Article, Controlled Study, Drug Clearance, Drug Distribution, Human, Human Cell, In Vitro Study, In Vivo Study, Incubation Time, Isotope Labeling, Ligand Binding, Mouse, Nonhuman, Priority Journal, Radioactivity, Tumor Xenograft, Cell Strain 3t3, Computer Assisted Emission Tomography, Evaluation, Metabolic Clearance Rate, Methodology, Nude Mouse, Scintiscanning, Squamous Cell Carcinoma, Tissue Distribution, Tumor Cell Line, 3t3 Cells, Sincalide, Emission-Computed
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale Delle Ricerche, Naples, Italy
Dipartimento di Chimica Biologica, Centro Interuniversitario Per la Ricerca Sui Peptidi Bioattivi, Università Federico II, Naples, Italy
Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, Italy
Dipartimento di Scienze Biomorfologiche e Funzionali, Universitá Federico II, Naples, Italy
References: Not available.
In vitro and in vivo evaluation of In-111-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging
UNLABELLED: Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging and therapy. Receptors of the cholecystokinin family have been shown to be overexpressed in different types of neuroendocrine tumors. The purposes of this study were to evaluate the cholecystokinin octapeptide amide (CCK8) peptide tagged with a diethylenetriaminepentaacetic acid derivative (DTPAGlu) and to test whether a (111) In-labeled conjugate ((111) In-DTPAGlu-G-CCK8, a derivative containing the chelating agent DTPAGlu bound through a glycine linker at the N-terminal end of the bioactive peptide CCK8) is suitable for cholecystokinin-B receptor (CCKBR) imaging.; METHODS: CCK8 was synthesized by solid-phase techniques and covalently coupled to DTPAGlu through a glycine linker at its amino terminus. The compound was labeled with (111) In. The radiochemical purity and stability of the compound were assessed by chromatographic methods. NIH-3T3 and A431 cells overexpressing CCKBR were used to characterize the in vitro properties of the compound. Nude mice bearing control and CCKBR-overexpressing A431 xenografts were used as an in vivo model.; RESULTS: DTPAGlu-G-CCK8 showed rapid and efficient labeling with (111) In. The radiolabeled conjugate showed specific binding to both cell lines overexpressing CCKBR. Binding was saturable, with a dissociation constant of approximately 20 nmol/L in both cell systems. Both cell lines showed internalization of the ligand after interaction with the receptor. Biodistribution studies showed rapid localization of (111) In-DTPAGlu-G-CCK8 on CCKBR-overexpressing A431 xenografts that was severalfold higher than that on control tumors at all time points tested. Unbound activity showed rapid clearance of over 80% through the kidneys by 30 min after injection. The labeled peptide conjugate was very stable in serum but showed a rapid breakdown after injection. Incubation with kidney homogenates suggested that most breakdown occurred in the kidneys, favoring the clearance of unbound activity.; CONCLUSION: Our findings indicate that the in vitro and in vivo characteristics of (111) In-DTPAGlu-G-CCK8 are favorable for CCKBR imaging, as the peptide shows high-affinity binding to the receptor, is internalized in CCKBR-expressing cells, and shows avid uptake in CCKBR-overexpressing xenografts, with rapid clearance of unbound radioactivity through the kidneys. Furthermore, the ease of synthesis, high labeling efficiency, and chemical stability of DTPAGlu make this chelating moiety an ideal candidate for widespread use in peptide radiolabeling for nuclear medicine applications
In vitro and in vivo evaluation of In-111-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(661 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote