A step ahead to enhancing routine breast cancer resection: Spheroid and hen's egg chorioallantoic membrane models to assess the photodynamic diagnosis efficiency of ALA and PSI-ALA-hex.

Aminolevulinic acid (ALA) and its derivatives have been used in the diagnosis of several diseases through topical, intravesical, and oral administration. However, their intravenous use for the theranostics of cancers has not raised interest despite its potential advantages. In this study, we compared the efficacy of ALA, its hexyl ester ALA-Hex, and our new derivative PSI-ALA-Hex to induce a fluorescent protoporphyrin IX (PpIX) overproduction in breast cancers. First, we tested the drugs on four subtypes of breast cancer spheroids in vitro. Our results demonstrated the capacity of ALA-Hex and PSI-ALA-Hex to produce PpIX in all breast spheroids, although ALA struggled in half of the models. We applied the chick embryo in vivo model to investigate the intravenous administration route of ALA and PSI-ALA-Hex, ALA-Hex being toxic. We engrafted breast cancer nodules having various hormonal profiles onto the chorioallantoic membrane of the eggs. They were all detected by fluorescence imaging with mild efficacy using PSI-ALA-Hex, which displayed a maximum selectivity of 2.2 to 2.9, whereas ALA showed a higher selectivity from 3.2 to 5.1 at 300 μmol/kg. PSI-ALA-Hex was less appropriate for the diagnosis of breast cancer by intravenous administration. We show for the first time, to the best of our knowledge, the photodetection and imaging of a wide range of breast tumors in vivo upon intravenous treatment with ALA.