Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10 1

Evaluation of cancer-therapy efficacy at early time points is necessary for realizing the goal of delivering maximally effective treatment. Molecular imaging with carefully selected tracers and methodologies can provide the means for realizing this ability. Many therapies are aimed at inducing apoptosis in malignant tissue; thus, the ability to quantify apoptosis in vivo may be a fruitful approach. Apoptosis rate changes occur on a fast time scale, potentially allowing correspondingly rapid decisions regarding therapy value. However, quantification of tissue status based on apoptosis imaging is complicated by this time scale and by the spatial heterogeneity of the process. Using the positron emission tomography (PET) tracer 2-(5-fluoro-pentyl)-2-methyl-malonic acid (F-18 ML-10), we present methods of voxelwise analysis yielding quantitative measures of apoptosis changes, parametric apoptosis change images, and graphical representation of apoptotic features. A method of deformable registration to account for anatomic changes between scan time points is also demonstrated. Overall apoptotic rates deduced from imaging depend on tumor density and the specific rate of apoptosis, a situation resulting in an ambiguity in the source of observed image-based changes. The ambiguity may be resolved through multimodality imaging. An example of intracellular sodium magnetic resonance imaging coupled with F-18 ML-10 PET is provided.