title: Preclinical evaluation of radiolabeled DOTA-derivatized cyclic minigastrin analogs for targeting cholecystokinin receptor expressing malignancies.
abstract: OBJECTIVE
  Targeting of cholecystokinin receptor expressing malignancies such as medullary thyroid carcinoma is currently limited by low in vivo stability of radioligands. To increase the stability, we have developed and preclinically evaluated two cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-minigastrin analogs radiolabeled with (111)In and (68)Ga.
  
  
  METHODS
  Radiolabeling efficiency, in vitro characterization, cholecystokinin receptor subtype 2 (CCK-2) binding in human tumor tissues, and cell internalization on CCK-2 receptor expressing AR42J cells, as well as biodistribution and small animal imaging in two different mouse xenograft models were studied.
  
  
  RESULTS
  High receptor affinity and receptor-mediated uptake of the radioligands in AR42J cells was confirmed in vitro. (111)In-labeled cyclic DOTA-peptides showed a specific tumor uptake of ~1% ID/g in vivo,                            (68)Ga-labeled analogs of ~3% ID/g. Small animal SPECT imaging resulted to be superior with (111)In-DOTA-cyclo-MG2 in comparison with (111)In-DOTA-cyclo-MG1.
  
  
  CONCLUSIONS
  Cyclic DOTA-minigastrin analogs are promising candidates for gastrin receptor scintigraphy and targeted radionuclide therapy.
authors: Department of Nuclear Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria. elisabeth.vonguggenberg@uki.at
authors: Elisabeth
authors: E
authors: von Guggenberg
authors: Christine
authors: C
authors: Rangger
authors: Jane
authors: J
authors: Sosabowski
authors: Peter
authors: P
authors: Laverman
authors: Jean-Claude
authors: JC
authors: Reubi
authors: Irene Johanna
authors: IJ
authors: Virgolini
authors: Clemens
authors: C
authors: Decristoforo
mesh_terms: D000818:Animals; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D005260:Female; D005710:Gallium Radioisotopes; D005755:Gastrins / Q000737:chemistry / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D005710:Gallium Radioisotopes; D005755:Gastrins; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D011949:Receptors, Cholecystokinin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C008530:minigastrin