First evaluation of PET-based human dosimetry and biodistribution of [18F]FAZA, a tracer for imaging tumor hypoxia

Objectives Tumor hypoxia has a major negative predictive value for local tumor progression, likeliness of metastasis, and overall tumor prognosis in several types of human cancers. [18F]FAZA is a PET biomarker for non-invasive identification and quantification of regional tumor hypoxia, presenting a more favourable tumor-to-background ratio with respect to the widely used hypoxia tracer [18F]FMISO. However, no studies are actually available on [18F]FAZA human biodistribution and its dosimetry. Aim of the present study was to firstly evaluate in non-small cell lung cancer (NSCLC) patients the PET-based human dosimetry and biodistribution of [18F]FAZA.

Methods Five NSCLC patients referred to surgical treatment underwent whole body PET and CT scans after injection of 371±37 MBq of [18F]FAZA. Following 10-min dynamic imaging of the heart to calculate the activity in blood, four total body studies were acquired at 10, 64, 120 and 240 min post injection (PI). Urine samples were collected after each imaging session and at 360 min PI. Regions of interest were drawn around visually identifiable sources organs to generate time activity curves. Residence time were determined from these curves, and dose to individual organs and body as a whole were calculated using OLINDA/EXM 1.1.

Results Blood clearance was characterized by a rapid distribution phase, followed by a first order elimination phase. The main radiation source regions in [18F]FAZA distribution were bladder, kidney, liver, spleen, and muscle. The highest uptake was found in the muscle and liver with a peak of 42.7±5.3% and 5.3±0.6% of injected activity, respectively. The total urinary excretion was 4.5±1.2 MBq of injected activity. The highest absorbed dose was to the bladder wall (0.019 mGy/MBq with 2 hours voiding interval) and liver (0.001 mGy/MBq). The effective dose (ED) was 0.0098±0.0014 mSv/MBq.

Conclusions The estimate [18F]FAZA ED for 370 MBq injection is 3.7 mSv that is lower than that reported for [18F]FMISO (4.4 mSv). This finding is in line with literature of preclinical studies that show a lower half-life in the normal tissue of [18F]FAZA with respect to [18F]FMISO. The favorable radiation risk profile associated to whole body PET with [18F]FAZA is definitely feasible for clinical hypoxia evaluation, also allowing patients to safely receive consecutive PET/CT studies.