ESTRO 2024 - Abstract Book

S3929

Physics - Image acquisition and processing

ESTRO 2024

Results:

MRI-based quantification was not possible for patients P1, P2, P3 and P12 who did not benefit from VFA sequences. T1 signal change in GTVs revealed NPs accumulation of 12.7 μmol/L (range: 7.8 ± 0.5 – 21.6 ± 5.6 µmol/L) among the three patients (P4, P5, P6) treated at the first dose level (30 mg/kg). This concentration increased by 18% to 15.0 µmol/L (range: 5.2 ± 3.9 – 40.7 ± 4.8 µmol/L) for the five patients (from P7 to P11) receiving the second one (50 mg/kg). A significant quantity of NPs was also found in the bladder (up to 4 times higher than in the GTV) suggesting an excretion of the nanoagents by urine. No significant NPs concentration could be quantified in healthy peripheral tissues supporting the fact that NPs were passively deposited in the tumor exclusively by enhanced permeability and retention effect. The delineation of the GTV had a strong influence on the determination of the mean NPs concentration, with a mean inter-physician difference of 17.4% (considering MR1 and MR2 from P4 to P11). MR-based NPs concentrations were in agreement with the ICP-MS analyses, with concentrations of 9.9 ± 8.2 µmol/L for level 1 and 27.5 ± 13.7 µmoL/L for level 2. P9 absorbed 3 times more NPs than others who received the same dose and developed atypical local reactions after irradiation (radionecrosis). In the additional biopsies, no significant quantity of NPs was found, supporting a non-persistance of the NPs in the tumor several months after irradiation. Based on the 3D cell model experiments, the potential of the NPs was highlighted, with radio-enhancement effects of about 15 % at 2 Gy for both modalities.

Conclusion:

Even if further follow-up of patients in this and subsequent clinical trials will be necessary to assess the reliability of this proof of concept, this study opens the way to the integration of a dose modulation factor to better take into account the impact of NPs in radiotherapy. Correlation between uptake and toxicities underscores the needs for retention quantification to be able to anticipate complications and precisely adjust the prescription before radiotherapy delivery.

Keywords: nanoparticles; T1 mapping, 3D cell models