Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells

Nucl Med Biol. 2001 Jan;28(1):13-23. doi: 10.1016/s0969-8051(00)00176-1.


In developing radioiodinated agents for pancreatic and brain tumor imaging by single photon emission tomography (SPET), we prepared p-amino-3-[123I]iodo-l-phenylalanine (IAPA), p-[123I]iodo-l-phenylalanine (IPA), L-8-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) in radiochemical yields up to 95%, and we investigated their uptake in human pancreatic carcinoma and glioblastoma cells as well as the mechanisms promoting the tumor uptake. The radiopharmaceutical uptake into tumor cells was rapid (t(1/2) < or = 5 min) and temperature- and pH-dependent. The radioactivity concentration in tumor cells varied from 10 to 33% of the total activity (105-310 cpm/1000 cells) following a 30-min incubation at 37 degrees C (pH 7.4). In comparison, accumulation of the radiopharmaceuticals into normal brain and pancreatic tissue remained relatively low. Depolarizing the plasma membrane potential in high K+ buffer significantly altered the radioactivity concentration in the tumor cells, suggesting that membrane potential plays a certain role in the cellular uptake. Competitive inhibition experiments with specific amino acid transport inhibitors indicated that the uptake of IAPA, IPA and IMT into human pancreatic carcinoma and glioblastoma cells is predominantly mediated by the L and ASC transport systems, while no substantial involvement of the transport system A in their tumor uptake could be demonstrated. In contrast, results of the present investigation indicated that ITIC is not taken up into tumor cells via the common neutral amino acid carrier systems, including the A, L and ASC system. Furthermore, preloading with naturally occurring L-amino acids failed to stimulate the cellular uptake of the radiopharmaceuticals. These data indicate that the investigated radiopharmaceuticals exhibit interesting characteristics with promise for in vivo tumor investigations to ascertain their potential as radioligands for glioma and pancreatic carcinoma imaging by SPET.

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / pharmacokinetics*
  • Animals
  • Biological Transport
  • Chromatography, High Pressure Liquid
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / metabolism*
  • Humans
  • Iodine Radioisotopes
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / metabolism*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tumor Cells, Cultured


  • Amino Acids
  • Iodine Radioisotopes
  • Radiopharmaceuticals