Brachytherapy approach using¹⁷⁷ Lu conjugated gold nanostars and evaluation of biodistribution, tumor retention, dosimetry and therapeutic efficacy in head and neck tumor model

Brachytherapy can provide sufficient doses to head and neck squamous cell carcinoma (HNSCC) with minimal damage to nearby normal tissues. In this study, the β⁻-emitter¹⁷⁷ Lu was conjugated to DTPA-polyethylene glycol (PEG) decorated gold nanostars (¹⁷⁷ Lu-DTPA-pAuNS) used in surface-enhanced Raman scattering and photothermal therapy (PTT). The accumulation and therapeutic efficacy of¹⁷⁷ Lu-DTPA-pAuNS were compared with those of¹⁷⁷ Lu-DTPA on an orthotopic HNSCC tumor model. The SPECT/CT imaging and biodistribution studies showed that¹⁷⁷ Lu-DTPA-pAuNS can be accumulated in the tumor up to 15 days, but¹⁷⁷ Lu-DTPA could not be detected at 24 h after injection. The tumor viability and growth were suppressed by injected¹⁷⁷ Lu-DTPA-pAuNS but not nonconjugated¹⁷⁷ Lu-DTPA, as evaluated by bioluminescent imaging. The radiation-absorbed dose of the normal organ was the highest in the liver (0.33 mSv/MBq) estimated in a 73 kg adult, but that of tumorsphere (0.5 g) was 3.55 mGy/MBq, while intravenous injection of¹⁷⁷ Lu-DTPA-pAuNS resulted in 1.97 mSv/MBq and 0.13 mGy/MBq for liver and tumorsphere, respectively. We also observed further enhancement of tumor-suppressive effects by a combination of¹⁷⁷ Lu-DTPA-pAuNS and PTT compared to¹⁷⁷ Lu-DTPA-pAuNS alone. In conclusion,¹⁷⁷ Lu-DTPA-pAuNS may be considered as a potential radiopharmaceutical agent for HNSCC brachytherapy.