Abstract B147: Tumor response imaging with [F-18] fluorothymidine (FLT).

Abstract

Abstract Background: Current cancer treatments have different mechanisms and variable responses in most histologic groups. The ability to determine treatment response at the molecular level by measuring tumor thymidine kinase 1 activity is being evaluated with FLT PET in groups of patients with different tumor histology. Methods: Under FDA IND approved protocols, patients treated on standard clinical and clinical trial protocols for glioblastoma, carcinoma brain metastases, breast cancer, and AML underwent quantitative PET imaging with FLT at baseline, mid-therapy, and post therapy. Dynamic acquisitions of the sites of known tumor were acquired for 60 minutes, followed by a whole-body static image survey. All images were reconstructed with CT attenuation correction. Regions of interest for the tumor, liver, and surrounding tissues were analyzed for uptake at each data time. Regional tissue FLT uptake was described as the tissue standard uptake variable (SUV), and FLT transport (K1) and flux using a compartmental model analysis. The tumor K1 values were generated to quantify FLT delivery to tumor. Comparisons were made between FLT-PET obtained at sequential times in individual patients and with clinical response. Results: At this time, 19 patients with primary brain tumors, 3 patients with brain metastases, 9 breast cancer patients, and 7 AML patients have been enrolled; at least one post-therapy image has been completed in all but 2 patients. The results have been analyzed semi-quantitatively as SUV and quantitatively by compartmental modeling to determine K1 and flux values for tumor baseline and post therapy comparisons. In most tumors, uptake by either SUV or flux declined in response to treatment but trends in tumor SUV values were not consistent with FLT flux values. In several cases, the FLT K1 and flux values were divergent, emphasizing the requirement to account for FLT delivery changes in observed tumor activity in response to therapy. This effect was most prominent in brain tumors and AML patients. Tumor blood flow/delivery is likely an independent response parameter that can be estimated from analysis of dynamic FLT PET. The poster will show evaluation of the predictive ability of baseline FLT studies as well as the role of pre/post comparisons. Conclusions: FLT PET imaging shows increased tumor uptake across several histologic types. This uptake decreases significantly with therapy, however the flow/delivery parameters and flux values from imaging are important uptake parameters to consider individually to understand changes in response to therapy. Supported by NIH/NCI P01 CA042045-23 and S10 RR017229. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B147. Citation Format: Janet F. Eary, Jeanne M. Link, Mark Muzi, Finbarr O'Sullivan, Jason K. Rockhill, James R. Fink, Hannah M. Linden, Kenneth A. Krohn. Tumor response imaging with [F-18] fluorothymidine (FLT). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B147.