18F-fluorothymidine (FLT)-PET and diffusion-weighted MRI for early response evaluation in patients with small cell lung cancer: a pilot study

Abstract

Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters

“…A clinical study in twelve non-small cell lung cancer patients also showed that [ 18 F]FLT was not correlated with ADC and that the spatial distribution of aggressive areas did not reveal any systemic relation [12]. Some further clinical reports investigated the spatial relation of glucose metabolism ([ 18 F]FDG) and water diffusivity (ADC).…”

“…A clinical study in twelve non-small cell lung cancer patients also showed that [ 18 F]FLT was not correlated with ADC and that the spatial distribution of aggressive areas did not reveal any systemic relation [ 12 ].…”