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

Abstract

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.