ISSN: 1838-7640Theranostics
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Theranostics 2018; 8(1):292-303. doi:10.7150/thno.22217 This issue Cite
Research Paper
Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases
1. CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom;
2. Department of Physics and Astronomy, Agnes Scott College, Decatur, GA, United States of America;
3. Departamento de Física Aplicada, Instituto de Física "Gleb Wataghin", UNICAMP, Campinas, Brazil;
4. Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, Caen, France.
* Joint first authors
Citation:
Falzone N, Ackerman NL, Rosales LdlF, Bernal MA, Liu X, Peeters SGJA, Soto MS, Corroyer-Dulmont A, Bernaudin M, Grimoin E, Touzani O, Sibson NR, Vallis KA. Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases. Theranostics 2018; 8(1):292-303. doi:10.7150/thno.22217. https://www.thno.org/v08p0292.htm
Other stylesAbstract
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 α-emitting radionuclides, 149Tb, 211At, 212Pb, 213Bi and 225Ac; β-emitting radionuclides, 90Y, 161Tb and 177Lu; and Auger electron (AE)-emitters 67Ga, 89Zr, 111In and 124I, 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 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.
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.
Keywords: radionuclides, VCAM-1, brain metastases
Citation styles
APA
Falzone, N., Ackerman, N.L., Rosales, L.d.l.F., Bernal, M.A., Liu, X., Peeters, S.GJA., Soto, M.S., Corroyer-Dulmont, A., Bernaudin, M., Grimoin, E., Touzani, O., Sibson, N.R., Vallis, K.A. (2018). Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases. Theranostics, 8(1), 292-303. https://doi.org/10.7150/thno.22217.
ACS
Falzone, N.; Ackerman, N.L.; Rosales, L.d.l.F.; Bernal, M.A.; Liu, X.; Peeters, S.GJA.; Soto, M.S.; Corroyer-Dulmont, A.; Bernaudin, M.; Grimoin, E.; Touzani, O.; Sibson, N.R.; Vallis, K.A. Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases. Theranostics 2018, 8 (1), 292-303. DOI: 10.7150/thno.22217.
NLM
Falzone N, Ackerman NL, Rosales LdlF, Bernal MA, Liu X, Peeters SGJA, Soto MS, Corroyer-Dulmont A, Bernaudin M, Grimoin E, Touzani O, Sibson NR, Vallis KA. Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases. Theranostics 2018; 8(1):292-303. doi:10.7150/thno.22217. https://www.thno.org/v08p0292.htm
CSE
Falzone N, Ackerman NL, Rosales LdlF, Bernal MA, Liu X, Peeters SGJA, Soto MS, Corroyer-Dulmont A, Bernaudin M, Grimoin E, Touzani O, Sibson NR, Vallis KA. 2018. Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases. Theranostics. 8(1):292-303.
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