Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts
| Autor: | Csaba Juhász, Neil V. Klinger, Hancheng Cai, Otto Muzik, Yangchun Xin, Sharon K. Michelhaugh, Sandeep Mittal, Thomas J. Mangner, Shaohui Zhang, Anthony R. Guastella, Lisa Polin |
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| Rok vydání: | 2016 |
| Předmět: |
Pathology
medicine.medical_specialty Biodistribution Kynurenine pathway Metabolic Clearance Rate Brain tumor Mice SCID Sensitivity and Specificity 030218 nuclear medicine & medical imaging Mice 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor Biomarkers Tumor medicine Animals Humans Tissue Distribution Radiology Nuclear Medicine and imaging Carbon Radioisotopes Indoleamine 2 3-dioxygenase Fluoroethyl Mice Inbred BALB C medicine.diagnostic_test Brain Neoplasms Chemistry Tryptophan Reproducibility of Results Human brain medicine.disease Molecular Imaging medicine.anatomical_structure Oncology Organ Specificity Positron emission tomography Positron-Emission Tomography 030220 oncology & carcinogenesis Tyrosine Female Radiopharmaceuticals |
| Zdroj: | Journal of Nuclear Medicine. 58:208-213 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.116.179994 |
| Popis: | Abnormal tryptophan metabolism via the kynurenine pathway (KP) is involved in the pathophysiology of a variety of human diseases including cancers. α-[11C]-methyl-L-tryptophan (11C-AMT) positron emission tomography (PET) imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of 11C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-[18F]fluoroethyl)-L-tryptophan (18F-FETrp) may be useful to assess tryptophan metabolism via the KP. In this study, we tested in vivo organ and tumor uptake and kinetics of 18F-FETrp in patient-derived xenograft mouse models and compared it with 11C-AMT uptake. Methods: Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with 18F-FETrp and 11C-AMT were performed on mice bearing human brain tumors 1-7 days apart. The biodistribution and tumoral standardized uptake values (SUVs) for both tracers were compared. Results:18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas 11C-AMT showed higher uptake in kidneys. Both tracers showed uptake in the xenograft tumors with a plateau ~30-min post-injection; however, 18F-FETrp showed higher tumoral SUV than 11C-AMT in all three tumor types tested. The radiation dosimetry for 18F-FETrp determined from the mouse data compared favorably to the clinical 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET tracer. Conclusion:18F-FETrp tumoral uptake, biodistribution and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly-applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors. |
| Databáze: | OpenAIRE |
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