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

早期脑转移瘤VCAM-1靶向治疗的放射性核素剂量学评估

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作者:Nadia Falzone, Nicole L Ackerman, Liset de la Fuente Rosales, Mario A Bernal, Xiaoxuan Liu, Sarah Gja Peeters, Manuel Sarmiento Soto, Aurélien Corroyer-Dulmont, Myriam Bernaudin, Elisa Grimoin, Omar Touzani, Nicola R Sibson, Katherine A Vallis

Conclusion

MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of α-, β- and AE-emitting radionuclides for TRT. 212Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.

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 β- and α-emitters, 177Lu and 212Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions.

Results

177Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 µm. The DSB yield of 212Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV α-emissions from decay products, 212Bi and 212Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212Pb may be more effective for short range targeting of early micrometastatic lesions than 177Lu.

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