PT - JOURNAL ARTICLE AU - Corinne Beinat AU - Chirag Patel AU - Tom Haywood AU - Lewis Naya AU - Jessa Castillo AU - Bin Shen AU - Tarik Massoud AU - Andrei Iagaru AU - Guido Davidzon AU - Lawrence Recht AU - Sanjiv Gambhir TI - Initial Clinical Evaluation of [<sup>18</sup>F]DASA-23, a PET Imaging Tracer for Evaluation of Aberrantly Expressed Pyruvate Kinase M2 in Glioblastoma DP - 2021 May 01 TA - Journal of Nuclear Medicine PG - 99--99 VI - 62 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/62/supplement_1/99.short 4100 - http://jnm.snmjournals.org/content/62/supplement_1/99.full SO - J Nucl Med2021 May 01; 62 AB - 99Introduction: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain, making it an important biomarker of cancer glycolytic re-programming. We describe the translation and initial clinical evaluation of a novel positron emission tomography (PET) tracer 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in patients with GBM. Methods: [18F]DASA-23 was synthesized under current Good Manufacturing Practices United States Food and Drug Administration (FDA) oversight with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity of &gt;95%. In a phase I trial (NCT03539731), we administered [18F]DASA-23 to n=4 healthy male and n=4 healthy female adult volunteers to study its whole body biodistribution, radiation dosimetry, and brain kinetics using simultaneous PET/MRI. Dynamic brain [18F]DASA-23 PET/MRI scans were also performed in a pilot cohort of patients with intracranial tumors (n=10). Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated. Results: In healthy human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. The tracer was cleared through the bladder and also showed uptake in the gallbladder, liver, and intestines over time (Fig. 1a). In healthy volunteers’ brain dynamic scans, [18F]DASA-23 exhibited high initial uptake (SUV ~5) in most brain structures, including cerebral cortex and the posterior fossa, followed by washout over the 60 min acquisition period (Fig. 1b). In patients with intracranial malignancies, [18F]DASA-23 successfully visualized contrast-enhancing tumors with a trend towards increasing uptake with increasing tumor grade (Fig. 1c). In a GBM patient, [18F]DASA-23 SUVmean and SUVmax were 2.0 and 2.2, respectively. The absence of PKM2 within healthy brain resulted in a high tumor-to-brain ratio (TBR) of 2.5 and a TBRmax of 2.8. Conclusion: We developed and translated [18F]DASA-23 as a promising new tracer that enables visualization of aberrantly expressed PKM2 for the first time in human subjects. The uptake of [18F]DASA-23 was elevated in GBMs compared to normal brain. Owing to low levels of PKM2 in healthy brain, a promising application of [18F]DASA-23 will likely be in the detection of early glycolytic response to therapy in GBM patients. Together, these results encourage further clinical studies to evaluate the utility of [18F]DASA-23 PET in human subjects. Acknowledgements: This work was supported by the Ben and Catherine Ivy Foundation, GE Healthcare, and Stanford ChEM-H.