Expression of L amino acid transport system 1 and analysis of iodine-123-methyltyrosine tumor uptake in a pancreatic xenotransplantation model using fused high-resolution-micro-SPECT-MRI.

Abstract

BACKGROUND:

The specificity in discriminating pancreatitis is limited in the positron emission tomography (PET) using Fluorine-18-fluorodeoxyglucose. Furthermore, PET is not widely available compared to the single photon emission computed tomography (SPECT). Since amino acids play a minor role in metabolism of inflammatory cells, the potential of the SPECT tracer, 3-[123I]iodo-L-alpha-methyltyrosine (123I-IMT), for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice.

METHODS:

123I-IMT was injected to eight mice inoculated with subcutaneous or orthotopic pancreatic tumors. Fused high-resolution-micro-SPECT (Hi-SPECT) and magnetic resonance imaging were performed. The gene expression level of L amino acid transport-system 1 (LAT1) was analyzed and correlated with tumor uptake of 123I-IMT.

RESULTS:

A high uptake of 123I-IMT was detected in all tumor-bearing mice. The median tumor-to-background ratio (T/B) was 12.1 (2.0-13.2) for orthotopic and 8.4 (1.8-11.1) for subcutaneous xenotransplantation, respectively. Accordingly, the LAT1 expression in transplanted Colo357 cells was increased compared to non-malignant controls.

CONCLUSIONS:

Our mouse model could show a high 123I-IMT uptake in pancreatic cancer. Fused MRI scans facilitate precise evaluation of uptake in the specific regions of interest. Further studies are required to confirm these findings in tumors derived from other human pancreatic cancer cells. Since amino acids play a minor role in the metabolism of inflammatory cells, the potential for application of 123I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.

• Authors: Corinna von Forstner, Maaz Zuhayra, Ole Ammerpohl, Yi Zhao, Sanjay Tiwari, Olav Jansen, Holger Kalthoff, Eberhard Henze, Jan-Hendrik Egberts
• Journal: Hepatobiliary & pancreatic diseases international : HBPD INT (Hepatobiliary Pancreat Dis Int) Vol. 10 Issue 1 Pg. 30-7 (Feb 2011) ISSN: 1499-3872 [Print] Singapore
• PMID: 21269932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Transport System L
• Amino Acids
• Iodine Radioisotopes
• Methyltyrosines
• Radiopharmaceuticals
• 3-iodo-alpha-methyltyrosine

Topics

• Adenocarcinoma (diagnostic imaging, genetics, metabolism)
• Amino Acid Transport System L (genetics, metabolism)
• Amino Acids (metabolism)
• Animals
• Cell Line, Tumor
• Female
• Gene Expression
• Humans
• Iodine Radioisotopes (pharmacokinetics)
• Magnetic Resonance Imaging (methods)
• Methyltyrosines (pharmacokinetics)
• Mice
• Mice, SCID
• Pancreatic Neoplasms (diagnostic imaging, genetics, metabolism)
• Radiopharmaceuticals (pharmacokinetics)
• Tomography, Emission-Computed, Single-Photon (methods)
• Transplantation, Heterologous