Purpose: Gold nanoparticles (GNPs) are promising targeted radiosensitizers due to their capability of specific tumor uptake and locally deposited high dose. This study evaluated the dose enhancement of PSMA-targeted GNPs in prostate cancer radiotherapy at megavoltage energy. Moreover, we investigated the impact of depth-induced spectrum change on radiosensitization, to explore the potential of beam modification in clinical GNP-assisted radiotherapy.
Methods: 15-nm PEGylated GNPs were conjugated to anti-PSMA antibodies using 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxy sulfosuccinimide. LNCaP prostate cancer cells were pretreated with 250µg/mL PSMA-targeted GNPs. Cells were irradiated with 160kV x-rays on RadSource small-animal irradiator, to verify the dose enhancement with GNPs at kV energy and offer reference to MV irradiation group. To evaluate GNP-aided dose enhancement at MV energy, LNCaP cells were treated using a 6MV flattening-filtered photon beam from Varian Trilogy LINAC with by 20cm×20cm field size. Cells located in culture plates were sandwiched in Elasto-gel bolus (1.0cm thick) and covered by solid water with different thickness to mimic tumors at different depths (1.5cm, 5cm, 10cm, and 20cm). A 5cm-thickness solid water was placed under the plate for backscatter along with OSLDs for dose confirmation. Radiation dose enhancement by GNPs was assessed via clonogenic assay, and quantification of DNA double-strand break via γ-H2AX foci counting.
Results: Under 2Gy-irradiation, clonogenic assay revealed statistically significant GNP-induced dose enhancement with kV beam (150%) and MV beam (140%) at 2.5cm depth. Additionally, γ-H2AX showed statistically significantly increased foci counts under 2Gy-kV (125%) and 2Gy-MV-2.5cm (120%) irradiation, respectively. Clonogenic assay of LNCaP cells at varying depth from MV irradiation showed increased radiosensitization at 20cm depth.
Conclusion: PSMA-targeted GNPs are effective radiosensitizers for prostate cancer cells irradiated with both kV and MV beams. Furthermore, beam quality plays a critical role in optimizing GNP-induced radiosensitization on prostate cancer cells.