Imaging Proliferation of Stage IV Cutaneous Melanoma With 18 F-FLT PET/CT : A Potential Noninvasive Tool for Predicting Treatment Resistance to Targeted Therapy?

Abstract

18 F-FLT PET/CT visualizes cellular proliferation and may correlate more directly with tumor aggressiveness and treatment response than 18 F-FDG PET/CT in melanoma patients treated with BRAF/MEK inhibitors. We aimed to assess whether 18 F-FLT PET/CT can predict early resistance to BRAF/MEK inhibitors in addition to current clinical tools in patients with BRAF-mutated metastatic melanoma. This explorative side study of the phase II multicenter REPOSIT trial included 19 patients with stage IV BRAF V600E/K-mutated cutaneous melanoma who underwent optional 18 F-FLT PET/CT. 18 F-FLT PET/CT was performed at baseline and after 2 weeks of treatment to evaluate baseline uptake and early changes in metabolic activity. 18 F-FDG PET/CT was performed at baseline for comparison. Ki67 expression was assessed in metastatic tissue samples. Analyses included: (1) visual comparison of baseline 18 F-FLT and 18 F-FDG uptake, (2) correlation of 18 F-FLT uptake with Ki-67, (3) semiquantitative analysis of baseline 18 F-FLT uptake, and (4) evaluation of percentage change in 18 F-FLT uptake after 2 weeks. Patients with consistently lower 18 F-FLT than 18 F-FDG uptake in metastases had longer progression-free survival (PFS; median 9.6 months, range: 3.4 to 32.3) compared with those with equal/higher or heterogeneous 18 F-FLT uptake (3.5 to 5.3 mo). Baseline 18 F-FLT SULpeak did not correlate with Ki67 expression ( P = 0.601), nor was Ki67 associated with PFS ( P = 0.39). No significant PFS difference was observed between patients with baseline 18 F-FLT SULpeak below or above the median ( P = 0.601). However, a greater percentage decrease in 18 F-FLT uptake at 2 weeks was associated with longer PFS (median: 13.9 vs 4.3 mo, P = 0.005). Baseline 18 F-FLT uptake patterns relative to 18 F-FDG, and early changes in 18 F-FLT uptake, were associated with PFS in patients treated with BRAF/MEK inhibitors. These explorative findings suggest that 18 F-FLT PET/CT may have predictive value, warranting confirmation in larger prospective studies.