RT Journal Article SR Electronic T1 Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 973 OP 980 DO 10.2967/jnumed.106.038570 VO 48 IS 6 A1 Roswitha Beck A1 Barbara Röper A1 Janette Maria Carlsen A1 Marc Cornelis Huisman A1 Julia Aloisia Lebschi A1 Nicolaus Andratschke A1 Maria Picchio A1 Michael Souvatzoglou A1 Hans-Jürgen Machulla A1 Morand Piert YR 2007 UL http://jnm.snmjournals.org/content/48/6/973.abstract AB We evaluated the predictive value of PET using the hypoxia tracer 18F-fluoroazomycin arabinoside (18F-FAZA) for success of radiotherapy in combination with tirapazamine, a specific cytotoxin for hypoxic cells. Methods: Imaging was performed on EMT6 tumor-bearing nude mice before allocating mice into 4 groups: radiochemotherapy (RCT: 8 fractions of 4.5 Gy within 4 d combined with tirapazamine, 14 mg/kg), radiotherapy alone (RT), chemotherapy alone (tirapazamine) (CHT), or control. Treatment success was assessed by several tumor growth assays, including tumor growth time from 70 to 500 μL and absolute growth delay (aGD). The median pretreatment 18F-FAZA tumor-to-background ratio served as a discriminator between “hypoxic” and “normoxic” tumors. Results: The mean tumor growth was significantly accelerated in hypoxic control tumors (growth time from 70 to 500 μL, 11.0 d) compared with normoxic control tumors (growth time from 70 to 500 μL, 15.6 d). Whereas RT delayed tumor growth regardless of the level of hypoxia, an additive beneficial therapeutic effect of tirapazamine to RT was observed only in hypoxic tumors (aGD, 12.9 d) but not in normoxic tumors (aGD, 6.0 d). Conclusion: This study provides compelling evidence that hypoxia imaging using 18F-FAZA PET is able to predict the success of RCT of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent tirapazamine. Pretreatment 18F-FAZA PET, therefore, offers a way for the individualization of tumor treatment involving radiation. The data suggest that by reserving hypoxia-directed therapy to tumors with high 18F-FAZA uptake, improvement of the therapeutic ratio is possible, as the therapeutic effect of tirapazamine seems to be restricted to hypoxic tumors.