AI Article Synopsis
- The spatial distribution of radiopharmaceuticals in multicellular clusters affects their biological response, complicating predictions in micrometastases.
- Researchers analyzed nonuniform activity distributions in tumor spheroids treated with actinium-225-DOTA liposomes and used this data for dose distribution and response prediction via MIRDcell V3.11.
- Results showed that MIRDcell predicted biological responses accurately for certain liposome types, although one type with different properties did not fit this trend.
Article Abstract
Purpose: 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 (Ac-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.
Methods: Four types of liposomes were prepared having membranes with different combinations of release (R) and adhesion (A) properties. The combinations were RA, RA, RA, and RA. These afford different penetrating properties into tissue. The liposomes were loaded with either carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) or Ac. 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 mean Ac 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 with Ac-liposomes.
Results: The biological responses of the multicellular clusters treated with Ac-liposomes with physicochemical properties RA, RA, and RA were predicted by MIRDcell with statistically significant accuracy. The prediction for RA was not predicted accurately.
Conclusion: In most instances, MIRDcell predicts responses of spheroids treated with Ac-liposomes that result in different tissue-penetrating profiles of the delivered radionuclides.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529908 | PMC |
| http://dx.doi.org/10.1007/s00259-022-05878-7 | DOI Listing |
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