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

• Published in: Hepatobiliary & pancreatic diseases international 2011-02, Vol.10 (1), p.30-37
• Main Authors: von Forstner, Corinna, Zuhayra, Maaz, Ammerpohl, Ole, Zhao, Yi, Tiwari, Sanjay, Jansen, Olav, Kalthoff, Holger, Henze, Eberhard, Egberts, Jan-Hendrik
• Format: Article
• Language: English
• Subjects: acid; adenocarcinoma; Adenocarcinoma - diagnostic imaging; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; amino; Amino Acid Transport System L - genetics; Amino Acid Transport System L - metabolism; Amino Acids - metabolism; Animals; Cell Line, Tumor; ductal; Endocrinology & Metabolism; Female; Gastroenterology and Hepatology; Gene Expression; high-resolution-micro-SPECT; Humans; Iodine Radioisotopes - pharmacokinetics; iodine-123-methyltyrosine; L amino acid transport-system 1; Magnetic Resonance Imaging - methods; Methyltyrosines - pharmacokinetics; Mice; Mice, SCID; pancreatic; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Radiopharmaceuticals - pharmacokinetics; Tomography, Emission-Computed, Single-Photon - methods; Transplantation, Heterologous; transport-system; xenotransplantation; xenotransplantation model
• ISSN: 1499-3872
• DOI: 10.1016/S1499-3872(11)60004-0

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-[ 123 I]iodo-L-α-methyltyrosine(123I-IMT),for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice. METHODS: 123 I-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 123 I-IMT. RESULTS:A high uptake of 123 I-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 123 I-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 123 I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.