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

Fluorine-18 labelled fluoroazomycinarabinoside ((18)F-FAZA) is a positron emission tomography (PET) biomarker for non-invasive identification of regional tumor hypoxia. Aim of the present Phase I study was to firstly evaluate in non-small cell lung cancer patients the human biodistribution and dosimetry of (18)F-FAZA. Methods: Five patients awaiting surgical resection after histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled for the study. The patients underwent a PET/computed tomography (CT) study after the injection of 371±32 MBq of (18)F-FAZA. The acquisition protocol consisted of a 10-minutes dynamic imaging of the heart to calculate the activity in blood, followed by four whole body PET/CT scans, from the vertex to mid-thigh, at: 10, 60, 120 and 240-minutes post-injection. Urine samples were collected after each imaging session and at 360-minutes post-injection. Volumes of interest were drawn around visually identifiable sources organs to generate time-activity-curves (TACs). Residence time were determined from TACs and effective dose (ED) to individual organs and whole body were calculated using OLINDA/EXM 1.2 for standard male and female. Results: Blood clearance was characterized by a rapid distribution phase, followed by a first order elimination phase. The highest uptakes were found in muscle and liver with peaks of 42.7±5.3% and 5.5±0.6% of injected activity, respectively. The total urinary excretion was 15% of the injected activity. The critical organ was urinary bladder wall with the highest radiation-absorbed doses of 0.047±0.008 mGy/MBq and 0.067±0.007 mGy/MBq calculating on 2 and 4 hours voiding intervals. The ED for standard male and female was 0.013±0.004 mSv/MBq and 0.014±0.004 mSv/MBq depending on the voiding schedule. Conclusion: With respect to available literature, the biodistribution of (18)F-FAZA appeared to be slightly different in humans than in mice, with a low clearance in humans. Therefore, estimated organ radiation doses from animal data could exhibit a moderate underestimation. Our data showed that dosimetry of (18)F-FAZA, for an injection of 370 MBq of tracer, is safe for its clinical use and it is almost similar to other widely used PET ligands. In particular, the ED is not appreciably different from those obtained with other hypoxia tracers, such as (18)F-fluoromisonidazole ((18)F-FMISO).

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Feb 16 [Epub ahead of print]

Savi Annarita, Elena Incerti, Federico Fallanca, Valentino Bettinardi, Francesca Rossetti, Cristina Monterisi, Antonia Compierchio, Giampiero Negri, Piero Zannini, Luigi Gianolli, Maria Picchio

IRCCS San Raffaele Scientific Institute, Italy., University of Milano-Bicocca.