UTILITY OF 6- [18F]-L-FLUORO-L-3, 4-DIHYDROXYPHENYLALANINE POSITRON EMISSION TOMOGRAPHY-MAGNETIC RESONANCE IMAGING (18F-DOPA PET-MRI) METRICS AS A BIOMARKER FOR TREATMENT ASSESSMENT IN SARCOMA PATIENTS

Summary: A critical strategy in the effective treatment of cancer is identifying noninvasive techniques, such as imaging biomarkers, for early assessment of therapeutic response to minimize the toxicities and economic burden of ineffective therapy, and to increase disease-free and overall survival. Determining correlative prognostic metrics of early treatment response with recurrence and survival using non-invasive techniques may have a significant impact on the care of sarcoma patients as well as clinical trial end points. Conventional imaging is inadequate to predict response to therapy in sarcoma patients. Although a decrease in tumor volume is the eventual goal of neoadjuvant therapy, quantitative measurement of tumor volume not an adequate early and predictive biomarker of response or outcome. Amino acid PET tracer metrics are showing promise as independent biomarkers of sarcoma patient survival and early response assessment. By way of glucose metabolism, 18F-FDG PET metrics have had significant success as a biomarker in sarcoma imaging. Alternative PET tracers are now being developed and investigated to take advantage of non-glucose metabolites to reveal information about sarcoma tumor biology that may have diagnostic or prognostic implications. Sarcoma tumor cells upregulate amino acid transport, transmethylation rate, and protein synthesis. Radiolabeled amino acids are absorbed and incorporated into proteins that can serve as a marker of protein synthesis. Since this is a recent and active area of research, limited studies are available in the literature. Amino acid tracers have shown superiority for differentiating fibrosarcoma from inflammatory background. In addition, these tracers have been able to predict outcomes based on changes in imaging before and up to one month after treatment in patients after carbon ion radiotherapy in bone osteosarcomas and soft tissues sarcomas from changes in imaging before and up to one month following treatment. These studies also showed prognostic value in 2-year survival with pre-treatment and post-treatment imaging, independently evaluated. In Ewing’s sarcoma, increased LAT1 (L-type amino acid transporter 1) expression at the cell surface can differentiate from inflammatory lesions.