| Abstract: |
Purpose: To demonstrate that positron emission tomography (PET) with fluorine 18 (F-18) fluorthanatrace (FTT) depicts activated poly (adenosine diphosphate-ribose) polymerase (PARP) expression and is feasible for clinical trial evaluation. Materials and Methods: All studies were conducted prospectively from February 2012 through July 2015 under protocols approved by the local animal studies committee and institutional review board. The area under the receiver operating characteristic curve (AUC, in g/mL (.) min) for F-18-FTT was assessed in normal mouse organs before and after treatment with olaparib (n = 14), a PARP inhibitor, or iniparib (n = 11), which has no PARP inhibitory activity. Murine biodistribution studies were performed to support human translational studies. Eight human subjects with cancer and eight healthy volunteers underwent imaging to verify the human radiation dosimetry of F-18-FTT. The Wilcoxon signed rank test was used to assess for differences among treatment groups for the mouse studies. Results: In mice, olaparib, but not iniparib, significantly reduced the F-18-FTT AUC in the spine (median difference before and after treatment and interquartile range [IQR]: -17 g/ mL (.) min and 10 g/mL (.) min, respectively [P =.0001], for olaparib and -3 g/mL (.) min and 13 g/mL (.) min [P =.70] for iniparib) and in nodes (median difference and interquartile range [IQR] before and after treatment: -23 g/ mL (.) min and 13 g/mL (.) min [P =.0001] for olaparib; -9 g/mL (.) min and 17 g/mL (.) min [P =.05] for iniparib). The effective dose was estimated at 6.9 mSv for a 370-MBq F-18-FTT dose in humans. In humans, the organs with the highest uptake on images were the spleen and pancreas. Among five subjects with measurable tumors, increased F-18-FTT uptake was seen in one subject with pancreatic adenocarcinoma and another with liver cancer. Conclusion: The results suggest that F-18-FTT uptake reflects PARP expression and that its radiation dosimetry profile is compatible with those of agents currently in clinical use. (C) RSNA, 2016 |
