An exploratory study of volumetric analysis for assessing tumor response with (18)F-FAZA PET/CT in patients with advanced non-small-cell lung cancer (NSCLC)

Abstract

Background: Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as (18)F-fluoroazomycin arabinoside ((18)F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG). The purpose of this study was to study the effects of chemotherapy on (18)F-FAZA and (18)F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients

Methods: At baseline and after the second chemotherapy cycle, both PET/CT with (18)F-FDG and (18)F-FAZA was performed in seven patients with metastasized NSCLC. (18)F-FAZA and (18)F-FDG scans were aligned with deformable image registration using Mirada DBx. The primary tumors were contoured, and on the (18)F-FDG scan, volumes of interest (VOI) were drawn using a 41 % adaptive threshold technique. Subsequently, the resulting VOI was transferred to the (18)F-FAZA scan. (18)F-FAZA maximum tumor-to-background (T/Bgmax) ratio and the fractional hypoxic volume (FHV) were assessed. Measurements were corrected for partial volume effects. Finally, a voxel-by-voxel analysis of the primary tumor was performed to assess regional uptake differences.

Results: In the primary tumor of all seven patients, median (18)F-FDG standard uptake value (SUVmax) decreased significantly (p = 0.03). There was no significant decrease in (18)F-FAZA uptake as measured with T/Bgmax (p = 0.24) or the FHV (p = 0.35). Additionally, volumetric voxel-by-voxel analysis showed that low hypoxic tumors did not significantly change in hypoxic status between baseline and two cycles of chemotherapy, whereas highly hypoxic tumors did. Individualized volumetric voxel-by-voxel analysis revealed that hypoxia and metabolism were not associated before and after 2 cycles of chemotherapy.

Conclusions: Tumor hypoxia and metabolism are independent dynamic events as measured by (18)F-FAZA PET and (18)F-FDG PET, both prior to and after treatment with chemotherapy in NSCLC patients.

Keywords: 18F-FAZA; 18F-FDG; Chemotherapy; NSCLC.

Fig. 1

Per patient comparison of regional voxel distribution in the primary tumor of ¹⁸F-FAZA (T/Bg, vertical axis) versus ¹⁸F-FDG (SUV, horizontal axis) at baseline and after 2 cycles of chemotherapy. The horizontal axis represents the ¹⁸F-FDG uptake in SUV. The vertical axis represents the ¹⁸F-FAZA uptake in tumor-to-background ratio. Blue represents voxel distribution assessed at baseline, while green represents voxel distribution assessed after 2 cycles of chemotherapy. ¹⁸F-FDG data of patient 4 was not available after 2 cycles of chemotherapy

Fig. 2

Difference between two cycles of chemotherapy and baseline was assessed for ¹⁸F-FAZA T/Bg (a) and ¹⁸F-FDG SUV (b) in the all primary tumor voxels of seven (¹⁸F-FAZA) and six (¹⁸F-FDG) patients, respectively. a The vertical line in figure (a) denotes the hypoxic cutoff of 1.4 T/Bg. Areas above 1.4 T/Bg are considered hypoxic. A decrease in ¹⁸F-FAZA activity can be seen as a result of treatment, yet this is not so clear compared to ¹⁸F-FDG. The decrease in ¹⁸F-FAZA activity is, however, most pronounced in the most hypoxic areas. b Per patient, different cutoff values are seen, due to the use of the 41 % adoptive threshold technique in selecting tumor areas. A clear decrease in ¹⁸F-FDG activity in almost all tumor voxels as a result of treatment. Although the decrease is clear overall, the decrease is most pronounced in areas with initially the highest ¹⁸F-FDG uptake