Initial results of hypoxia imaging using 1-alpha-D: -(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18F-FAZA).
OBJECTIVE
Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-alpha-D: -(5-deoxy-5-[(18)F]-fluoroarabinofuranosyl)-2-nitroimidazole ((18)F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study.


METHODS
Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of (18)F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal (18)F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded.


RESULTS
Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of (18)F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of (18)F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased (18)F-FAZA uptake in the primary lung tumour. No side effects of the administration of (18)F-FAZA were observed.


CONCLUSIONS
This study suggests that (18)F-FAZA may be a very useful radiopharmaceutical to image hypoxia in the tumour types selected. Especially the high uptake by gliomas was encouraging. Given the good imaging properties, including acceptable T/B ratios in the tumour categories studied, (18)F-FAZA could be considered as a very promising agent for assessing the hypoxic fraction of these tumour types.
Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada. epostema@ualberta.ca
Ernst J
EJ
Postema
Alexander J B
AJ
McEwan
Terence A
TA
Riauka
Piyush
P
Kumar
Dacia A
DA
Richmond
Douglas N
DN
Abrams
Leonard I
LI
Wiebe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging; D005260:Female; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging; D008223:Lymphoma / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging*; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D055815:Young Adult
D005462:Fluorine Radioisotopes; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside