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Efficacy of Systemic Radionuclide Therapy with p-¹³¹I-Iodo-L-Phenylalanine Combined with External Beam Photon Irradiation in Treating Malignant Gliomas

¹ Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany; ² Department of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany; ³ Department of Neuropathology, Friedrich-Schiller University, Jena, Germany; ⁴ Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Homburg, Germany; and ⁵ Department of Experimental Neurosurgery, Saarland University Medical Center, Homburg, Germany

Correspondence: For correspondence or reprints contact: Samuel Samnick, Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Strasse 6, D-97080, Würzburg, Germany. E-mail: Samnick_S{at}klinik.uni-wuerzburg.de

p-¹³¹I-iodo-L-phenylalanine (¹³¹I-IPA) is a tumor-specific amino acid derivative that demonstrated antiproliferative and tumoricidal effects on experimental gliomas. This study tested the efficacy of ¹³¹I-IPA combined with external beam photon radiotherapy as a new therapeutic approach against gliomas. Methods: Glioma cells derived from the rat F98 glioma or human Tx3868 or A1207 glioblastoma cell lines were stereotactically inoculated into the brains of Fischer 344 rats or RNU rats. Tumor formation was verified radiologically. On day 8, groups of glioma-bearing rats of each tumor model underwent whole-brain radiotherapy with 8 Gy, an intravenous administration of ¹³¹I-IPA (30 MBq), or combined treatment, aiming for a total of 12 rats per group. Another 12 animals were treated with physiologic saline and served as control. Results: Control rats had a combined median survival (±SD) of 21 ± 6 d. All revealed metabolically and histologically large tumor masses. Efficacy of radiotherapy alone or a monotherapy with 30 MBq of ¹³¹I-IPA was statistically insignificant on the syngeneic Fischer–F98 model (P 0.45 and P = 0.10, respectively). In contrast, a subset of long-term survivors (>120 d) was observed in RNU rats bearing Tx3868 and A1207 glioblastoma xenografts (18%–25% and 35%–45% for radiotherapy and ¹³¹I-IPA, respectively). Combined ¹³¹I-IPA and radiotherapy treatment significantly prolonged median survival for the syngeneic Fischer–F98 glioma model (P < 0.01) and human glioblastoma–bearing RNU rats alike (P < 0.05). On day 120 after monotherapy with ¹³¹I-IPA, 45% of the RNU rats were still alive, but after 8 Gy of photon radiotherapy only 18%–25% of the RNU and none of the Fischer rats survived. In comparison, 55%–75% survival rates were registered after combined treatment on day 120 for all animal models. Conclusion: These data convincingly demonstrated that systemic radionuclide therapy with ¹³¹I-IPA combined with external photon radiotherapy is a safe and highly effective treatment for experimental gliomas, which may merit a clinical trial to ascertain its potential in patients with gliomas. Because only a low ¹³¹I-IPA activity and low radiotherapy doses were applied, further optimizations including higher radiation doses and conventional fractionated radiotherapy are warranted.

Key Words: malignant gliomas • targeted radionuclide therapy • external photon radiotherapy • combination treatment • radiosensitivity

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