Preclinical evaluation of 68Ga-DOTA-minigastrin for the detection of cholecystokinin-2/gastrin receptor-positive tumors

Mol Imaging. 2011 Apr;10(2):144-52.

Abstract

In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor-mediated uptake (p = .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Cholecystokinin / metabolism*
  • Chromatography, High Pressure Liquid
  • Coordination Complexes*
  • Drug Screening Assays, Antitumor / methods*
  • Gastrins*
  • Inhibitory Concentration 50
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism*
  • Peritoneal Neoplasms / diagnostic imaging
  • Peritoneal Neoplasms / pathology
  • Positron-Emission Tomography
  • Rats
  • Receptor, Cholecystokinin B / metabolism*
  • Subcutaneous Tissue / diagnostic imaging
  • Subcutaneous Tissue / pathology
  • Tissue Distribution

Substances

  • 68Ga-DOTA-minigastrin
  • Coordination Complexes
  • Gastrins
  • Receptor, Cholecystokinin B
  • minigastrin
  • Cholecystokinin