Assessment of the efficacy of targeted PDA-66 therapy in a PC-3 Prostate Cancer Xenograft Model using [ ¹⁸  F]FDG and [ ¹⁸  F]FLT PET/CT and MRI

Ziel/Aim In prostate cancer (PC) the development and evaluation of novel targeted therapies play an emerging role potentially improving outcome. Multimodal imaging for therapy response assessment (TRA) of these new drugs is a promising tool to evaluate efficacy. Herein we evaluate the in-vivo efficacy of the indolylmaleimide PDA-66 using small animal F-18 FDG, F-18 FLT PET/CT and MRI in a PC-3 human PC xenograft mouse model. Anti-tumoral effects of PDA-66 were demonstrated in-vitro previously.

Methodik/Methods We carried out F-18 FDG and F-18 FLT PET/CT combined with morphological and DWI MRI for PDA-66 TRA in 22 PC-3 xenograft mice (treatment/controls: i.p. 4/4; i.v. 3/3; i.t. 4/4/; 100–150 mg/kg BW daily, seven days). PC-3 cells were implanted subcutaneously in the flanks of 129S4-Rag2 mice. 4–6 weeks post xenografting mice underwent dynamic F-18 FDG and FLT PET/CT (injection of 15 and 10 MBq, respectively) and MRI before and 1, 2, and 3 weeks after start of treatment. Image analysis was performed using VOIs (tumour, muscle, liver, kidney and blood) calculating %ID/g as well as tumor volumes and ADC values. Additionally, tumors and organs were collected for pharmacokinetic analyses.

Ergebnisse/Results Between baseline and follow up scans a stable/slightly increased F-18 FDG and F-18 FLT uptake accompanied by increased tumor volumes and stable ADC values was observed in both PDA-66 treated as well as control mice. No significant differences in F-18 FDG and F-18 FLT uptake, tumor volumes or ADC values between treatment and control groups were detected at the 5 timepoints.

Schlussfolgerungen/Conclusions These in-vivo results showed that the applied PDA-66 regimen did not induce the previously observed in-vitro effects in the in-vivo model. Currently pharmacokinetic analyses are employed to characterise PDA-66 uptake and clearing.