Clinical application of a population-based input function (PBIF) for a shortened dynamic whole-body FDG-PET/CT protocol in patients with metastatic melanoma treated by immunotherapy

Background: The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF), instead of an image-derived input function (IDIF) across the 60-min post-injection period, and study its effect on the FDG influx rate (Ki) quantification in patients with metastatic melanoma (MM) undergoing immunotherapy.Methods: Thirty-seven patients were enrolled, including a PBIF modeling group (n = 17) and an independent validation cohort (n = 20) of MM from the ongoing prospective IMMUNOPET2 trial. All dWB-PET data were acquired on Vision 600 PET/CT systems. The PBIF was fitted using a Feng's 4-compartments model and scaled to the individual IDIF tail's section within the shortened acquisition time. The area under the curve (AUC) of PBIFs was compared to respective IDIFs AUC within 9 shortened time windows (TW) in terms of linear correlation (R-2) and Bland-Altman tests. Ki metrics calculated with PBIF vs IDIF on 8 organs with physiological tracer uptake, 44 tumoral lesions of MM and 11 immune-induced inflammatory sites of pseudo-progression disease were also compared (Mann-Whitney test).Results: The mean +/- SD relative AUC bias was calculated at 0.5 +/- 3.8% (R-2 = 0.961, AUC(PBIF) = 1.007 x AUC(IDIF)). In terms of optimal use in routine practice and statistical results, the 5th-7th pass (R-2 = 0.999 for both Ki mean and Ki max) and 5th-8th pass (mean +/- SD bias = - 4.9 +/- 6.5% for Ki mean and - 4.8% +/- 5.6% for Ki max) windows were selected. There was no significant difference in Ki values from PBIF5_7 vs IDIF5_7 for physiological uptakes (p > 0.05) as well as for tumor lesions (mean +/- SD Ki IDIF5_7 3.07 +/- 3.27 vs Ki PBIF5_7 2.86 +/- 2.96 100ml/ml/min, p = 0.586) and for inflammatory sites (mean +/- SD Ki IDIF5_7 1.13 +/- 0.59 vs Ki PBIF5_7 1.13 +/- 0.55 100ml/ml/min, p = 0.98).Conclusion: Our study showed the feasibility of a shortened dWB-PET imaging protocol with a PBIF approach, allowing to reduce acquisition duration from 70 to 20 min with reasonable bias. These findings open perspectives for its clinical use in routine practice such as treatment response assessment in oncology.