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Radiation Therapy of Small Cell Lung Cancer with ¹⁷⁷Lu-DOTA-Tyr³-Octreotate in an Animal Model

¹ Department of Radiation Physics, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
² Department of Pathology, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
³ Department of Surgery, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
⁴ Institute of Nuclear Medicine, University Hospital, Basel, Switzerland

Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using ¹¹¹In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr³-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), labeled with the medium-energy electron emitter ¹⁷⁷Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model. Methods: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with ¹⁷⁷Lu-DOTA-Tyr³-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr³-octreotate and another control group was not treated. Results: In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with ¹⁷⁷Lu-DOTA-Tyr³-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 ± 0.004. Conclusion: Radiation therapy with ¹⁷⁷Lu-DOTA-Tyr³-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with ¹⁷⁷Lu-DOTA-Tyr³-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.

Key Words: radionuclide therapy • ¹⁷⁷Lu-DOTA-Tyr³-octreotate • small cell lung cancer • nude mice

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