title: In vitro and in vivo characterization of three 68Ga- and 111In-labeled peptides for cholecystokinin receptor imaging.
abstract: Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], are suitable for imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], and DOTA-MG0, labeled with (111)In or (68)Ga, was evaluated in BALB/c nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK2R-expressing tumors. Both (111)In-DOTA-sCCK8 and (111)In-DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK2R-positive tumors.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Roosenburg
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.forename: Lieke
authors.initials: L
authors.lastname: Joosten
authors.forename: Annemarie
authors.initials: A
authors.lastname: Eek
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
authors.forename: Floris L
authors.initials: FL
authors.lastname: van Delft
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D043887:Receptor, Cholecystokinin B / Q000032:analysis / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals; D043887:Receptor, Cholecystokinin B; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid