Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases

作者：Falzone Nadia^*; Ackerman Nicole L; Rosales Liset de la Fuente; Bernal Mario A; Liu Xiaoxuan; Peeters Sarah G J A; Soto Manuel Sarmiento; Corroyer Dulmont Aurelien; Bernaudin Myriam; Grimoin Elisa; Touzani Omar; Sibson Nicola R; Vallis Katherine A

来源：Theranostics, 2018, 8(1): 292-303.

DOI：10.7150/thno.22217

• radionuclides
• VCAM-1
• brain metastases

Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of a-emitting radionuclides, Tb-149, At-211, Pb-212, Bi-213 and Ac-225; beta-emitting radionuclides, Y-90, Tb-161 and Lu-177; and Auger electron (AE)-emitters Ga-67, Zr-89, In-111 and I-124, for targeted radionuclide therapy (TRT).
METHODS: Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative beta- and alpha-emitters, Lu-177 and Pb-212. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions.
RESULTS: Lu-177 produced 2.69 +/- 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 mu m. The DSB yield of Pb-212 included two local maxima produced by the 6.1 MeV and 8.8 MeV alpha-emissions from decay products, Bi-212 and Po-212, with yields of 7.64 +/- 0.12 and 9.15 +/- 0.24 per GbpGy, respectively. Given its higher DSB yield Pb-212 may be more effective for short range targeting of early micrometastatic lesions than Lu-177.
CONCLUSION: MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of alpha-, beta- and AE-emitting radionuclides for TRT. Pb-212, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.

• 出版日期2018