Combined use of [18F]ML-10 PET and Bound Sodium MRI Biomarkers for Therapy Response Assessment of Glioblastoma Multiforme.

1419 Objectives Apoptosis imaging may provide a means to evaluate therapeutic efficacy very early after therapy start. A challenge to developing quantitative methodology is that apoptosis imaging provides a measure of tumoral apoptotic rate at the time of scan acquisition, but information provided with regard to cumulative therapeutic effect over a long time is uncertain given the ephemeral nature of the apoptosis process. An increase in volume fraction bound sodium concentration (vBSC), measured via MRI, between therapy assessment times, has been associated with tumor proliferation between scan time points. We compared changes in 18F-labeled 2-(5-fluoro-pentyl)-2-methyl-malonic acid ([18F]ML-10) standard uptake values (SUV) with changes in vBSC between baseline and 2 post-therapy time points in a cohort of glioblastoma multiforme (GBM) subjects to assess the predictive value of early [18F]ML-10 PET for determining late changes in vBSC. Methods N = 4 GBM (3 newly diagnosed; 1 recurrent) subjects receiving concomitant radiation and temozolomide chemotherapy were studied with PET and MRI at baseline (BL; ~5 days before therapy), and at 2 therapy assessment times: early therapy assessment (ETA; ~15 days post therapy start) and late (FU; ~72 days post therapy start). PET data were acquired for 30 min on either a Siemens HR+ or Siemens integrated PET/MRI scanner starting 120 min after injection of 10 mCi of [18F]ML-10. [18F]ML-10 uptake was quantified using SUV. Sodium MRI scans were acquired using a Siemens 3T Magnetom Tim Trio MRI scanner (approximately 15 min after completion of same time point [18F]ML-10 PET) with a dual-tuned (1H-23Na) head coil for a total acquisition time of 22 min to acquire two 3D single-quantum (SQ) sodium images at two echo times. vBSC was quantified through pixel-by-pixel subtraction of the SQ sodium images using an integrated calibration. Time-to-progression (TTP) post therapy initiation was used as the subject outcome measure. Results We were able to acquire and quantify vBSC and [18F]ML-10 uptake near simultaneously at 3 clinically relevant time points in 4 subjects. Subject 1 demonstrated a pronounced increase in [18F]ML-10 SUV from BL to ETA (0.45 to 0.68), with a corresponding decrease in vBSC between BL and FU (42.91 mM to 32.42 mM), consistent with increased apoptotic cell death and decreased proliferation (TTP = 12). The tumor region for subject 2 became rapidly necrotic (TTP = 19 months), and demonstrated both a decrease in [18F]ML-10 SUV from BL to ETA (1.16 to 0.84), and a decrease in vBSC from BL to FU (61.19 mM to 27.31 mM). Subject 3 showed pronounced downward change in [18F]ML-10 SUV between BL and ETA (0.93 to 0.52) and low vBSC at BL (21.55 mM) and FU (26.71 mM) with no new progression to date (TTP > 22 months). Subject 4 exhibited a slight decrease in [18F]ML-10 SUV between BL and ETA (0.34 to 0.32) with low to near background vBSC at BL (22.04 mM) and FU (27.09 mM) and rapid progression (TTP Conclusions The feasibility for near simultaneous acquisition and quantification of vBSC MRI and [18F]ML-10 PET on GBM subjects is demonstrated. Early (ETA compared to BL) [18F]ML-10 changes were compared with late (FU compared to BL) vBSC changes. 3 out of 4 subjects analyzed showed an inverse relationship between early [18F]ML-10 and late vBSC changes. Interpretation of vBSC and [18F]ML-10 scans acquired at the same post-therapy time points should keep in mind that apoptosis imaging likely provides an indication of tumor apoptotic rate close to the imaging time, while vBSC change provides a measure of cumulative therapeutic effect.