Data from A Clinical PET Imaging Tracer ([&lt;sup&gt;18&lt;/sup&gt;F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma

Jun Hyung Park,Israt S Alam,Samantha T Reyes,Guido Davidzon,Melanie Hayden-Gephart,Pauline Chu,Harsh Gandhi,Reena Thomas,Kim Halbert,Joy Q He,Rahul Sinha,Daniel Dan Liu,Andrei Iagaru,Michelle L James,Seema Nagpal,Corinne Beinat,Lawrence D Recht,Dawn Holley,Jessa B Castillo,Pablo Buccino,Chirag B Patel,Eli Johnson,Tarik F Massoud,Donald E Born,Monica Granucci,Lewis Naya,Megan Phillips,Mary Ellen I Koran,Bin Shen,Surya Murty,Tom Haywood,Mehdi Khalighi ,Geoffrey Warnock ,Naoshige Uchida ,Irving L Weissman ,Sanjiv S Gambhir

doi:10.1158/1078-0432.c.6531230

Data from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma

Jun Hyung Park, Israt S Alam + Show 34 more

Open Access

PDF Available

https://doi.org/10.1158/1078-0432.c.6531230

Copy DOI

Export

Save

Cite

Publication Date: Mar 31, 2023

License type: CC BY 4.0

Abstract
Full-Text PDF
Similar Papers

Abstract

Listen

<div>AbstractPurpose: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. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM.Experimental Design:[18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma.Results:In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation.Conclusions:We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.</div>

Full Text