64 Cu-Intraperitoneal Radioimmunotherapy: A Novel Approach for Adjuvant Treatment in a Clinically Relevant Preclinical Model of Pancreatic Cancer.

Autor:	Yoshii Y; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan yoshii.yukie@qst.go.jp., Matsumoto H; Nihon Medi-Physics Co., Ltd., Chiba, Japan; and., Yoshimoto M; Division of Functional Imaging, National Cancer Center Hospital East, Chiba, Japan., Oe Y; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Zhang MR; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Nagatsu K; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Sugyo A; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Tsuji AB; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Higashi T; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2019 Oct; Vol. 60 (10), pp. 1437-1443. Date of Electronic Publication: 2019 Mar 08.
DOI:	10.2967/jnumed.118.225045
Abstrakt:	Pancreatic cancer (PC) has a very poor prognosis. Surgery is the primary treatment for patients with resectable PC; however, local recurrence, hepatic metastasis, and peritoneal dissemination often occur even after extensive surgery. Adjuvant chemotherapy, typically with gemcitabine, has been used clinically but with only a modest survival benefit. To achieve a better outcome, we investigated the efficacy of 64 Cu-intraperitoneal radioimmunotherapy (ipRIT) with 64 Cu-labeled antiepidermal growth factor receptor antibody cetuximab as an adjuvant treatment after PC surgery using an orthotopic xenografted mouse model. Methods: The efficacy of adjuvant 64 Cu-ipRIT was investigated in a human PC mouse model harboring orthotopic xenografts of xPA-1-DC cells. To reproduce the clinical situation, PC xenografts were surgically resected when pancreatic tumors were readily visible but not metastatic tumors. Increasing doses of 64 Cu-cetuximab were intraperitoneally injected, and the mice were monitored for toxicity to determine the safe therapeutic dose. For adjuvant 64 Cu-ipRIT, the day after tumor resection, the mice were intraperitoneally administered 22.2 MBq of 64 Cu-PCTA-cetuximab and the survival was compared with that in surgery-only controls. For comparison, adjuvant chemotherapy with gemcitabine was also examined using the same model. Results: The mouse model not only developed primary tumors in the pancreas but also subsequently reproduced local recurrence, hepatic metastasis, and peritoneal dissemination after surgery, which is similar to the manifestations that occur with human PC. Adjuvant 64 Cu-ipRIT with 64 Cu-labeled cetuximab after surgery effectively suppressed local recurrence, hepatic metastasis, and peritoneal dissemination in this model. Significant improvement of the survival with minimal toxicity was achieved by adjuvant 64 Cu-ipRIT compared with that in control mice that underwent surgery only. Adjuvant chemotherapy with gemcitabine nominally prolonged the survival, but the effect was not statistically significant. Conclusion: 64 Cu-ipRIT with cetuximab can be an effective adjuvant therapy after PC surgery. (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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