Address reprint requests to: Bart De Spiegeleer; Faculty of Pharmaceutical Sciences, Ghent University, Harel- bekestraat 72, B-9000 Ghent, Belgium; Tel.: (32) 9- 2648100; Fax: (32) 9-2648193 E-mail: bart.despiegeleer@ugent.be CANCER BIOTHERAPY & RADIOPHARMACEUTICALS Volume 23, Number 2, 2008 © Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2007.0362 The Use of [ 123 I]-2-Iodo-L-Phenylalanine as an Early Radiotherapy Evaluation Tool: In Vitro R1M Rabdomyosarcoma Cell and In Vivo Mouse Experiments Veerle Kersemans, 1 Valentijn Vergote, 1 Virginie de Gelder, 2 Indira Madani, 2 Hubert Thierens, 2 Wilfried De Neve, 2 John Mertens, 3 Guido Slegers, 1 Christian Burvenich, 4 Kathelijne Peremans, 4 and Bart De Spiegeleer 1 1 Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium 2 Faculty of Medicine, Ghent University, Ghent, Belgium 3 Laboratory for Medical Imaging and Physics, Vrije Universiteit Brussels, Belgium 4 Faculty of Veterinary Sciences, Ghent University, Merelbeke, Belgium ABSTRACT This study was performed to determine whether [ 123 I]-2-iodo-L-phenylalanine single-photon emission com- puted tomography (SPECT) can be used to monitor the tumor response to radiotherapy in an early phase. Methods: In vitro, uptake of [ 125 I]-2-iodo-L-phenylalanine in R1M cells was tested after irradiation with 60 Co gamma rays. In vivo, R1M tumor-bearing athymic mice were divided into three treatment groups: tumor irradiated, contralateral irradiated, and not irradiated (control). [ 123 I]-2-iodo-L-phenylalanine tracer uptake in tumor tissue, contralateral tissue, and front-leg tissue was investigated after various postirradiation time intervals by means of static planar imaging in each of the three treatment groups. Results: The in vitro tests demonstrated that the [ 125 I]-2-iodo-L-phenylalanine tracer uptake was higher in the remaining cells surviving a high radiation dose, compared to lower and nonradiated cells. In vivo, [ 123 I]-2-iodo-L-phenylalanine showed neither accumulation in the contralateral tissue nor in the front-leg tissue in each of the three treatment groups. Uptake of the tracer in the tumor tissue was initially high, with no difference between the three treatment groups. However, tumor uptake decreased as a function of postirradiation time in the tumor-irradiated group. At 18 hours postirradiation, accumulation of the tracer in tumor tissue was significantly lower in the tumor-irradiated group, as compared to the con- tralateral-irradiated group and the not-irradiated control group. Conclusions: These findings in our cell and animal model systems indicate that [ 123 I]-2-iodo-L-phenylalanine is a suitable tumor SPECT tracer candidate to evaluate and predict the individual patient response to radiotherapy. Key words: [ 123 I]-2-iodo-L-phenylalanine, radiolabeled amino acids, tumor imaging, radiotherapy re- sponse, bystander effect 192 INTRODUCTION The response of tumors to therapy is typically de- termined by the evaluation of the change in the size of the tumor as measured by magnetic reso-