Optimal Time of Single Static PET Scan to Determine Tumor Hypoxia with 18F-FMISO in Glioblastoma

Abstract

Glioblastoma Multiform (GBM) is the most aggressive tumor in the brain. The tumor is characterized by extremely rapid growth, hypoxia (reduced availability of oxygen) and necrosis. This study aimed to determine the best optimal time (or minimal time) for 18F-FMISO PET single scan imaging with the help of spectral analysis (SA). Imaging protocols involved a 15 min dynamic scan followed by 10 min static scans at 2 h, 3 h, and 4 h in order to allow uptake of 18F- FMISO in the tumors. We applied SA to decompose the PET images into their essential components of perfused tissue, hypoxic tissue and tissue blood volume. The ratio of hypoxia to the input function (IF) and the ratio of hypoxia to contralateral normal tissue at 180 min were defined as Tumor-to-Blood ratio (TBR180), and as Tumor-to-Normal tissue ratio (TNR180). The intersection of hypoxia component time-activity curve (TAC) with IF and with contralateral TAC determined the demarcation between perfusion and hypoxia, and the time corresponding to these intersections corresponded to the minimum of the times to acquire a single PET scan in the clinic to delimit hypoxia with enough contrast. The results showed the image at 15 min with multifocal uptake in different regions while at 2 h and above the volume of the tumor appeared confined to the same region. The mean of the minimal optimal time between blood and hypoxia and between perfusion and hypoxia were found as 89 ± 59 min and 105 ± 69 min, respectively. At this average of minimum of optimal times, TBR89 and TNR89 in the 9 subjects were almost similar, meaning that, the optimal time of 89 min gave a good discrimination of hypoxia with mean TBR89 and TNR89 as 1.72 ± 0.22 and 1.74 ± 0.19. For the comparison, TBR180 and TNR180 were 2.6 ± 0.49 and 2.0 ± 0.23. In conclusion, based on different tumor status, we demonstrated that the optimal time for 18F-FMISO single scan measurement is around 90 min instead of times of 3 h and above.