Molecular imaging of head and neck xenograft mouse model with [18F] ML-10 and bioluminescence imaging

Objectives A reliable index of apoptosis (programmed cell death) obtainable in a reproducible, minimally-invasive procedure (e.g. PET) could be a major component in cancer-therapy evaluation. Since apoptosis is ephemeral and there is ongoing native tumor apoptosis, a method to establish a baseline is important to assess changes attributable to therapy. Our study is aimed at providing such an index by determining the stability of baseline scan measures for tumor uptake of the novel PET ligand [18F] ML-10, a PET apoptosis tracer.

Methods We injected 8 BALB/c nude mice with 100,000 OSC19 human head and neck tumor cells at tip of tongue. PET-CT imaging was performed on days 6, 8, and 9 post tumor implantation using the Siemens Inveon PET/CT scanner. Bioluminescence imaging(BLI) was performed using a Lumina XR scanner (Perkin Elmer) on the same day as PET. For PET imaging, animals were injected with 200-300uCi [18F] ML-10 and PET imaging was performed 30 min post radiotracer injection. Qualitative and quantitative analysis of tumor uptake was performed using Inveon Research Workplace software. Calculated SUVmean per body weight was standardized to liver and blood pool. BLI was used to guide the location of tumor.

Results BLI was used to assess for the presence and localization of tumor as well as to look for local lymph node metastases. On bioluminescence imaging, tumor was present in all 8 mice. The SUVmean from the PET images was standardized to liver uptake. Average tumor to liver ratios for all tumors was 0.961, ranging from 0.829-1.274. Average standard deviation for the 3 baseline scans across all 8 mice was 0.108, with range from 0.02-0.24.

Conclusions BLI is an effective modality for localizing tumors at baseline, where targeted tracer uptake may be low. In our model, the apoptosis tracer [F18]-ML-10 has an average change of 11% across scans separated by close temporal exam times (within a 3 day window). Future [18F] ML-10 PET studies will measure apoptosis after chemotherapy treatment in the head and neck cancer mouse model.

Research Support This work was support by the US National Institutes of Health research grant U01 CA140230, as well as the UPCI shared resources award P30CA047904 and Depart. of Energy Grant DE SC0008833.