Table 2 Summary of clinical studies evaluating therapy response and their findings in lung cancer based on [18F]FLT-PET proliferative imaging
Reference | n | [18F]FLT/[18F]FDG LC primary Tumour uptake (SUV) | [18F]FLT/[18F]FDG different LC histotypes uptake (SUVmax) | Purpose | TNM Stage | Reference standard | Findings | |
|---|---|---|---|---|---|---|---|---|
Frings et al. 2013 [28] | 14 | Variable uptake | NA | Study effect of pemetrexed-induced TS-inhibition on [18F]FLT uptake 4Â h after pemetrexed administration | NA | Histopathology CT response | Changes in [18F]FLT uptake 4Â h after pemetrexed administration were not predictive for tumour response, TTP or OS | |
Crandall et al. 2017 [29] | 9 | Mean SUVmax: Baseline: 5.6 ± 2.0 Post-cycle 1 (day 15–21): 4.8 ± 2.5 Post-cycle 2 (day 36–42): 4.4 ± 2.3 | NA | Study early chemotherapeutic response in comparison with [18F]FDG | T1bN1M0 (n = 1); T1bN2M0 (n = 1); T2bN0M0 (n = 1); T2bN1M0 (n = 2); T3N0M0 (n = 2); T3N1M0 (n = 1); T3N2M0 (n = 1) | Histopathology CT response Ki-67 [18F]FDG | [18F]FLT did not show significant difference between anatomic responders and anatomic non-responders while [18F]FDG showed significant difference between these groups | |
McHugh et al. 2018 [30] | 4 | SUVmax from baseline in two patients:—64.7% and—54.3% | NA | Study the effect of dexamethasone on pemetrexed efficacy | NA | CT response | Decline of [18F]FLT uptake from baseline, with a variable response between individual tumour lesions | |
Vera et al. 2011 [31] | 5 | Mean SUVmax: Baseline: 4.7 During therapy: 2.2 | [18F]FLT: Baseline: ADC (n = 2): 4.64 SqCC (n = 2): 3.86 During therapy: ADC (n = 2): 2.24 SqCC (n = 2): 2.13 [18F]FDG: Baseline: ADC (n = 2): 7.76 SqCC (n = 2): 6.36 During therapy: ADC (n = 2): 3.24 SqCC (n = 2): 5.38 | Study radiotherapy responses in comparison with [18F]FDG and F-miso | TXN3 (n = 1);T2N2 (n = 1);T3N2 (n = 1);T4N2 (n = 1); T4N3 (n = 1) | Histopathology | A significant decrease in SUVmax during radiotherapy was observed for [18F]FLT and [18F]FDG but not for F-miso | |
Saga et al. 2011 [32] | 20 | Mean SUVmax: baseline: 1.54 3 months posttherapy: 0.35 | NA | Longitudinal study of the responses to carbon-ion radiotherapy | T1N0M0 (n = 9); T2N0M0 (n = 11) | Histopathology CT response | [18F]FLT uptake significantly decreased after treatment Basline [18F]FLT uptake of patients who developed recurrence and who died of LC were significantly higher than that of patients who did not (p = 0.008 and 0.007) | |
Trigonis et al. 2014 [33] | 16 | SUVmean: baseline: 2.2 ± 0.7 Response value: 1.6 ± 0.4 SUVmax: baseline: 5.3 ± 2.0 Response value: 4.1 ± 1.4 | NA | Study early radiotherapy response and test–retest variability | NA | Histopathology CT response | SUVmean decreased by 25% in the absence of volumetric change (p = 0.0001) after 5–11 radiotherapy fractions. Larger decrease of 40% was shown in metastatic nodes with 31% decrease in volume (p < 0.0001). Similar findings for SUVmax were found. SUVmean reproducibility (standard deviation [SD]: 8.9%) in primary tumours was better than SUVmax reproducibility (SD: 12.6%) | |
Everitt et al. 2009 [34] | 5 | SUVmax: mean reduction of 0.58 × baseline | [18F]FLT: Baseline: ADC (n = 1): 5.3 SqCC (n = 2): 8.25 LCC (n = 2): 5.15 [18F]FDG: Baseline: ADC (n = 1): 15 SqCC (n = 2): 17.15 LCC (n = 2): 9.4 | Establish [18F]FLT assessment of cell proliferation during chemoradiotherapy | T2N0M0 (n = 1); T2N2M0 (N = 1); T2N3M0 (n = 1); T3N2M0 (n = 2) | Histopathology | Decline of [18F]FLT uptake after chemotherapy in epithelial cancers and bone marrow (radiosensitive tissue) | |
Everitt et al. 2014 [35] | 20 | [18F]FLT Median SUVmax: baseline: 6; wk2: 3; wk4: 2 [18F]FDG Median SUVmax: baseline: 14; wk2: 10; wk4:10 | NA | Study early chemo-radiotherapeutic response in comparison with [18F]FDG | NA | Histopathology CT response | [18F]FLT is a more sensitive tracer for early treatment response than [18F]FDG | |
Everitt et al. 2017 [36] | 60 | NA | NA | Study relationship between chemo-radiotherapeutic responses and clinical outcomes in comparison with [18F]FDG | NA | [18F]FDG | Stable uptake of [18F]FLT at 2 wk after therapy was associated with longer OS and PFS compared with patients whose tumours demonstrated reduced or absent [18F]FLT uptake Paradoxical association between changes in [18F]FLT uptake and clinical outcomes. This could be due to weakening tumourocidal effect of radiotherapy with inhibitory effect of possibly chemotherapy (carboplatin and paclitaxel) | |
Yang et al. 2012 [37] | 68 | Mean SUVmax: 4.1 | Baseline: ADC (n = 30): 3.8 SqCC (n = 28): 5 | Study antiangiogenic therapy responses in comparison with MVD | NA | Histopathology Ki-67 MVD | [18F]FLT uptake was significantly correlated with MVD as reflected by CD105-MVD (r = 0.633, p = 0.000). Patients with lower [18F]FLT uptake and CD105-MVD values had significantly higher median survival times than patients with higher [18F]FLT uptake and CD105-MVD values (p = 0.046) | |
Scarpelli et al. 2018 [38] | 14 | Change in SUVmax: during angiogenic therapy: −11% After combination chemotherapy: −44% | NA | Study the sequential responses of angiogenic therapy followed by chemotherapy | NA | Histopathology | [18F]FLT uptake significantly decreased during therapy (p = 0.04) and after combination chemotherapy (p = 0.03) | |
Scarpelli et al. 2018 [39] | 33 | NA | NA | Study the sequential responses of angiogenic therapy followed by chemotherapy | NA | Histopathology | Tumour cell proliferation and vasculature were decreased 2Â weeks after therapy and increased one week after therapy break | |
Sohn et al. 2008 [40] | 31 | Mean SUVmax decline, 7 days posttherapy:—36.0% for responders versus -10.1% for nonresponder (-10.9% was ued as cutoff) | NA | Study early EGFR-TKI (gefitinib) therapy responses to predict clinical outcome | IV (n = 28) | CT response | [18F]FLT uptake significantly decreased 7 days after gefitinib therapy in responders. Responders had significantly longer TTP (p = 0.03) than non-responders | |
Mileshkin et al. 2011 [41] | 51 | [18F]FLT SUVmax: baseline: 2.5 [18F]FDG SUVmax: 5.63 | NA | Study early EGFR-TKI (erlotinib) therapy responses to predict clinical outcome in comparison with [18F]FDG | NA | CT response | PFS was predicted by both [18F]FLT and [18F]FDG 2wks and 8wks after therapy. OS was predicted by both tracers 8wks after therapy but by [18F]FDG only 2wk after therapy | |
Zander et al. 2011 [42] | 34 | [18F]FLT Mean SUVpeak: baseline: 3.47 week2: 3.12 [18F]FDG Mean SUVpeak: baseline: 6.94 week2: 6.03 | NA | Study early EGFR-TKI (erlotinib) therapy responses to predict clinical outcome in comparison with [18F]FDG | NA | CT response | [18F]FLT predicted PFS but not OS 6 wks after therapy, while [18F]FDG predicted PFS, OS 6 wks after therapy | |
Kahraman et al. 2011 [43] | 30 | NA | NA | Study early EGFR-TKI (erlotinib) therapy responses to predict clinical outcome in comparison with [18F]FDG | NA | CT response | Both [18F]FLT and FDG predicted PFS 1wk and 6wk after therapy | |
Scheffler et al. 2013 [44] | 40 | Mean SUVmax,pretherapy: 3.0 | [18F]FLT: Baseline: ADC (n = 29): 3.18 SqCC (n = 6): 3.53 LCC (n = 1): 1.9 [18F]FDG: Baseline: ADC (n = 29): 7.09 SqCC (n = 6) = 6.38 LCC (n = 1): 6.6 | Study the prognostic value of baseline uptake in patients treated with EGFR-TKI (erlotinib) in comparison with [18F]FDG | NA | Histopathology Ki-67 | [18F]FLT to prognostically stratify NSCLC patients treated with erlotinib as patients with low uptake had significantly longer survival times (p = 0.027) than patients with high uptake | |
Bhoil et al. 2014 [45] | 15 | NA | NA | Study TKI (gefitinib or erlotinib) therapy responses to predict clinical outcome in comparison with [18F]FDG | NA | CT response | Neither OS nor PFS were correlated with [18F]FLT but both correlated with [18F]FDG | |