Abstract
1094
Objectives: - [68Ga]P15-041 is a new PET radiotracer being investigated for measurement of in vivo osteoblastic activity. It has been shown to exhibit high affinity specific binding to bone with rapid clearance from soft tissue and may be suitable for static whole-body imaging of bone metastases [1]. The goals of this study were: (1) to determine the impact of the interval between injection and scan time on both lesion uptake and precision of the uptake measurement and (2) to assess the impact of injected dose on the precision of uptake measurements. The study was motivated by the need to optimize dose and injection-scan interval for future clinical trial investigations. Methods - Seven male subjects with confirmed prostate cancer and known or suspected metastatic disease were injected with [68Ga]P15-041 (median dose: 172 MBq, less than 1/2 of a clinical FDG dose; range: 115-232 MBq). Whole-body data were acquired on a Philips Ingenuity PET/CT scanner at 2-3 time points post-injection (4 subjects @ 90 and 180 min; 3 subjects @ 60, 120, and 150 min). The data were reconstructed with the clinical list-mode time-of-flight ordered subsets expectation maximization algorithm with post-filtering to reliably characterize the dependence of lesion uptake and precision on counts that track with dose. The precision of uptake measurements was assessed using ten replicate datasets that were generated by bootstrapping the original list-mode data. The data were also subsampled to emulate lower injected activities of 37, 74, and (for 2 subjects) 111 MBq. Maximum uptake was measured in 9-11 regions of focal uptake in each subject, and the % standard deviation (%SD) across the 10 replicates was determined for each lesion, scan start time, and activity level. In addition, the change in uptake with scan interval post-injection, which reflects the change in physiological uptake in the lesions, was calculated after decay-correction. Results - The variability of the maximum lesion uptake measurement increased with decreasing counts, as expected; however, the %SD was less than 10% for activities down to 74 MBq for all lesions. The uptake increased between 60 and 120 min by 30 ± 18% on average, with a smaller (6 ± 9%) increase from 120 to 150 min; the corresponding average %SD increased by 24 ± 37% from 60 to 120 min and 14 ± 40% from 120 to 150 min. For the subjects with scans at 90 and 180 min, the uptake increased by 14 ± 12% with an increase in %SD of 62 ± 66%. Since both uptake and variability were observed to increase with longer injection-scan interval, the contrast/precision ratio will be determined to assess this trade-off further. Conclusions - With post-filtering, the variability of maximum lesion uptake was less than 10% SD for all lesions down to activities of 74 MBq. Scanning starting at 90-120 min post-injection gives a good trade-off between uptake and precision. Additional work will include assessment of other metrics for optimizing the injection-scan interval such as target/background (i.e., normal bone) ratio and measurements in more subjects (up to 15). Support - This work was supported in part by National Institutes of Health grants R43-CA221580 and R01-CA113941. [1] D. Alexoff, R. Doot, D. Pryma, et al. Preliminary kinetic analysis of [68Ga]P15-041, a novel 68Ga labeled bisphosphonate, from first-in-human studies. J Nucl Med, 58 (supplement 1), abstract 388, 2017.