Development of a new radioligand for cholecystokinin receptor subtype 2 scintigraphy: from molecular modeling to in vivo evaluation

Bioorg Med Chem. 2010 Jul 15;18(14):5400-12. doi: 10.1016/j.bmc.2010.05.031. Epub 2010 May 19.

Abstract

To improve the targeting to tumors expressing the cholecystokinin receptor subtype 2 (CCK2R) with limited kidney uptake, we synthesized a novel cholecystokinin C-terminal tetrapeptide (CCK4)-based derivative conjugated to an original bipyridine-chelator (BPCA), 111In-BPCA-(Ahx)2-CCK4. To our knowledge this is the first CCK4-based radioligand that presents a high affinity for the CCK2R, a high and specific tumor uptake, a low renal accumulation and a very good visualization of tumors in vivo compared with an internal control, 111Indium-trans-cyclohexyldiethylenetriaminepenta-acetic acid-cholecystokinin octapeptide (111In-CHX-A''-DTPA-CCK8). These properties make 111In-BPCA-(Ahx)2-CCK4, a promising candidate for imaging and peptide receptor radionuclide therapy of CCK2R positive tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Mice
  • Mice, Nude
  • Models, Molecular
  • NIH 3T3 Cells
  • Neoplasms / diagnostic imaging*
  • Oligopeptides* / chemistry
  • Oligopeptides* / pharmacokinetics
  • Oligopeptides* / pharmacology
  • Pentetic Acid / analogs & derivatives
  • Radionuclide Imaging / methods*
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / pharmacokinetics
  • Radiopharmaceuticals* / pharmacology
  • Receptor, Cholecystokinin B / chemistry
  • Receptor, Cholecystokinin B / metabolism*

Substances

  • Oligopeptides
  • Radiopharmaceuticals
  • Receptor, Cholecystokinin B
  • Pentetic Acid