Predicting response of micrometastases with MIRDcell V3: proof of principle with 225Ac-DOTA encapsulating liposomes that produce different activity distributions in tumor spheroids

Autor: Sumudu Katugampola, Jianchao Wang, Aprameya Prasad, Stavroula Sofou, Roger W. Howell
Rok vydání: 2022
Předmět:
Zdroj: European Journal of Nuclear Medicine and Molecular Imaging. 49:3989-3999
ISSN: 1619-7089
1619-7070
Popis: The spatial distribution of radiopharmaceuticals within multicellular clusters is known to have a significant effect on their biological response. Most therapeutic radiopharmaceuticals distribute nonuniformly in tissues which makes predicting responses of micrometastases challenging. The work presented here analyzes published temporally dependent nonuniform activity distributions within tumor spheroids treated with actinium-225-DOTA encapsulating liposomes (sup225/supAc-liposomes) and uses these data in MIRDcell V3.11 to calculate absorbed dose distributions and predict biological response. The predicted responses are compared with experimental responses.Four types of liposomes were prepared having membranes with different combinations of release (R) and adhesion (A) properties. The combinations were Rsup-/supAsup-/sup, Rsup-/supAsup+/sup, Rsup+/supAsup-/sup, and Rsup+/supAsup+/sup. These afford different penetrating properties into tissue. The liposomes were loaded with either carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) orsup225/supAc. MDA-MB-231 spheroids were treated with the CFDA-SE-liposomes, harvested at different times, and the time-integrated CFDA-SE concentration at each radial position within the spheroid was determined. This was translated into meansup225/supAc decays/cell versus radial position, uploaded to MIRDcell, and the surviving fraction of cells in spherical multicellular clusters was simulated. The MIRDcell-predicted surviving fractions were compared with experimental fractional-outgrowths of the spheroids following treatment withsup225/supAc-liposomes.The biological responses of the multicellular clusters treated withsup225/supAc-liposomes with physicochemical properties Rsup+/supAsup+/sup, Rsup-/supAsup+/sup, and Rsup-/supAsup-/supwere predicted by MIRDcell with statistically significant accuracy. The prediction for Rsup+/supAsup-/supwas not predicted accurately.In most instances, MIRDcell predicts responses of spheroids treated withsup225/supAc-liposomes that result in different tissue-penetrating profiles of the delivered radionuclides.
Databáze: OpenAIRE
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