IMG-30. Parametric maps of tryptophan metabolism can improve detection of non-enhancing tumor regions in post-treatment glioblastoma: a [18]FETrp PET/MRI study

Abstract BACKGROUND Increased amino acid transport in gliomas allows imaging of metabolically active tumor volume by PET. Tryptophan analog PET radiotracers can provide additional information by tracking tumoral metabolism via the upregulated immunosuppressive tryptophan-kynurenine pathway. We tested the clinically feasible tryptophan analog PET tracer [18]F-fluoro-ethyl-L-tryptophan ([18]FETrp) for detecting post-treatment glioblastoma infiltration while using a non-invasive approach to generate parametric tryptophan metabolic maps and comparing them with static tracer uptake maps and contrast-enhanced MRI. METHODS Five patients (age: 22-67 years) with previously treated glioblastoma showing MRI signs of tumor progression underwent [18]FETrp PET imaging. A dynamic acquisition protocol was applied to sample the brain and blood pool non-invasively using the FlowMotion Multiparametric PET software (Siemens Healthineers). Parametric brain images of the unidirectional uptake rate constant (Ki), characterizing irreversible tryptophan trapping, were fused with static uptake maps and contrast-enhanced brain MRI. Voxels with elevated Ki and uptake values were defined (>2SD above mean values in contralateral normal brain), and their spatial association with contrast-enhanced volumes was characterized by their % volume overlap and the distance between their centroids. RESULTS A substantial spatial volume overlap of 66±12% (average centroid distance: 5mm) was observed between MRI contrast-enhancing regions and elevated static [18]FETrp uptake. The overlap between contrast-enhancing regions and elevated Ki metabolic volumes was lower (6±5%, p<0.001), with increased Ki areas extending deeper into non-enhancing brain (12mm average spatial separation). These non-enhancing areas with high Ki values showed new contrast-enhancement on subsequent MRI, consistent with tumor progression. CONCLUSIONS Areas of high tryptophan metabolism detected by [18]FETrp PET-derived parametric maps extend outside the contrast-enhancing glioblastoma mass in adjacent non-enhancing brain regions that can be missed or underestimated by static uptake images. [18]FETrp PET metabolic maps have the potential for enhanced detection of non-enhancing glioma infiltration for improved treatment targeting.