Keywords: Cholecystokinin Receptors, Indium-111, Neuroendocrine Tumors, Peptides, Technetium-99m, Cholecystokinin B Receptor, Cholecystokinin Octapeptide, Cysteine, Diphenylphosphinopropionylglycylcysteinylcholecystokinin Octapeptide Tc 99m, Glycine, Indium 111, Pentetic Acid, Pentetic Acid Glutamylglycine Cholecystokinin Octapeptide In 111, Radiopharmaceutical Agent, Technetium 99m, Unclassified Drug, Amino Terminal Sequence, Animal Cell, Animal Experiment, Animal Model, Cancer Cell, Cancer Cell Culture, Concentration Response, Conference Paper, Controlled Study, Drug Clearance, Drug Metabolism, Drug Receptor Binding, Drug Synthesis, Image Analysis, In Vitro Study, In Vivo Study, Isotope Labeling, Kidney Clearance, Mouse, Nonhuman, Priority Journal, Protein Expression, Protein Localization, Thyroid Medullary Carcinoma, Cell Line, Chromatography, High Pressure Liquid, Drug Stability, Indium Radioisotopes, Nude, Radionuclide Imaging, Sincalide, Tissue Distribution, Chemistry, Diagnostic Use, Pharmacokinetics, Methods,
Affiliations: *** IBB - CNR ***
Ist. di Biostrutture e Bioimmagini, CNR, Napoli, Italy
Dipto. di Sci. Biomorfolog. e Funz., Universita' Federico II, Napoli, Italy
Dipto. di Chimica Biologica e CIRPeB, Universita' Federico II, Napoli, Italy
Istituto Nazionale Tumori, Napoli, Italy
Dipto. di Scienze Farmaceutiche, Universita' di Padova, Padova, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy. luigaloj@unina.it,
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Reubi, J.C., Schaer, J.C., Waser, B., Cholecystokinin(CCK)-A and CCK-B/gastrin receptors in human tumors (1997) Cancer Res, 57, p. 1377
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Reubi, J.C., Waser, B., Schaer, J.C., Unsulfated DTPA- and DOTA-CCK analogs as specific high-affinity ligands for CCK-B receptor-expressing human and rat tissues in vitro and in vivo (1998) Eur J Nucl Med, 25, p. 481
Behr, T.M., Behe, M., Angerstein, C., Cholecystokinin-B/gastrin receptor binding peptides: Preclinical development and evaluation of their diagnostic and therapeutic potential (1999) Clin Cancer Res, 5, pp. 3124s
Behr, T.M., Jenner, N., Radetzky, S., Targeting of cholecystokinin-B/gastrin receptors in vivo: Preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin (1998) Eur J Nucl Med, 25, p. 424
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Mather, S.J., Chianelli, M., Radiolabelled cytokines (1996) Q J Nucl Med, 40, p. 290
Wank, S. A., G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors: An exemplary family (1998) Am J Physiol, 274, pp. G60
Reubi, J. C., Schaer, J. C., Waser, B., Cholecystokinin (CCK) -A and CCK-B/gastrin receptors in human tumors (1997) Cancer Res, 57, p. 1377
Anelli, P. L., Fedeli, F., Gazzotti, O., L-Glutamic acid and L-lysine as useful building blocks for the preparation of bifunctional DTPA-like ligands (1999) Bioconjug Chem, 10, p. 137
Reubi, J. C., Waser, B., Schaer, J. C., Unsulfated DTPA- and DOTA-CCK analogs as specific high-affinity ligands for CCK-B receptor-expressing human and rat tissues in vitro and in vivo (1998) Eur J Nucl Med, 25, p. 481
Behr, T. M., Behe, M., Angerstein, C., Cholecystokinin-B/gastrin receptor binding peptides: Preclinical development and evaluation of their diagnostic and therapeutic potential (1999) Clin Cancer Res, 5, pp. 3124s
Behr, T. M., Jenner, N., Radetzky, S., Targeting of cholecystokinin-B/gastrin receptors in vivo: Preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin (1998) Eur J Nucl Med, 25, p. 424
Wilson, A. A., Jin, L., Garcia, A., DaSilva, J. N., Carbon-11 labelled cholecystokininB antagonists: Radiosynthesis and evaluation in rats (2001) Life Sci, 68, p. 1223
Mather, S. J., Chianelli, M., Radiolabelled cytokines (1996) Q J Nucl Med, 40, p. 290
In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging
Cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with In-111 or Tc-99m for CCK-B receptor imaging. Derivatives of CCK8 were obtained by addition at the N-terminus in solid phase of a DTPA derivative (DTPAGlu) linked through a glycine spacer (DTPAGlu-G-CCK8) or cysteine, glycine and a diphenylphosphinopropionyl moiety (PhosGC-CCK8) for labeling with In-111 and 99mTc, respectively. CCK-BR overexpressing A431 cancer cell lines were utilized to characterize in vitro Properties of the two compounds as well as for generating xenografts in nude mice for in vivo characterization. Both In-111-DTPAGlu-G-CCK8 and (99m) TcPhosGC-CCK8 showed similar binding affinities for CCK-BR with dissociation constants of 20-40 nM, were internalized after interaction with the receptor and displayed prolonged cellular retention times. Specific in vivo interaction with the receptor of both CCK8 analogs was observed in our animal model In-111-DTPAGlu-G-CCK8 showed better target to non-target ratios, although it appeared to be rapidly metabolized after injection and activity cleared through the kidneys. Tc-99m-PhosGC-CCK8 was more stable in vivo but showed marked hepatobiliary clearance with resulting high background activity in the bowel. The rapid clearance and lower background obtained with 111In-DTPAGlu-G-CCK8 make this a better candidate for further development
In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-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(449 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