Calcium carbonate carriers for combined chemo- and radionuclide therapy of metastatic lung cancer

Abstract

Considering the clinical limitations of individual approaches against metastatic lung cancer, the use of combined therapy can potentially improve the therapeutic effect of treatment. However, determination of the appropriate strategy of combined treatment can be challenging. In this study, combined chemo- and radionuclide therapy has been realized using radionuclide carriers (¹⁷⁷Lu-labeled core-shell particles, ¹⁷⁷Lu-MPs) and chemotherapeutic drug (cisplatin, CDDP) for treatment of lung metastatic cancer. The developed core-shell particles can be effectively loaded with ¹⁷⁷Lu therapeutic radionuclide and exhibit good radiochemical stability for a prolonged period of time. In vivo biodistribution experiments have demonstrated the accumulation of the developed carriers predominantly in lungs. Direct radiometry analysis did not reveal an increased absorbance of radiation by healthy organs. It has been shown that the radionuclide therapy with ¹⁷⁷Lu-MPs in mono-regime is able to inhibit the number of metastatic nodules (untreated mice = 120 ± 12 versus¹⁷⁷Lu-MPs = 50 ± 7). The combination of chemo- and radionuclide therapy when using ¹⁷⁷Lu-MPs and CDDP further enhanced the therapeutic efficiency of tumor treatment compared to the single therapy (¹⁷⁷Lu-MPs = 50 ± 7 and CDDP = 65 ± 10 versus¹⁷⁷Lu-MPs + CDDP = 37 ± 5). Thus, this work is a systematic research on the applicability of the combination of chemo- and radionuclide therapy to treat metastatic lung cancer.

Keywords: Calcium carbonate; Cisplatin; Combined therapy; Core-shell particles; In vivo biodistribution; Lung cancer; Therapeutic radionuclides.