Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model.

Min-Ying Lin,Wen-Sheng Huang,Chun-Yi Wu,Yi-Jang Lee,Shinn-Ying Ho,Ting-Wen Chen,Nin-Chu Sheu,Hsin-Hua Hsieh,Jyh-Cheng Chen,Chuan-Lin Chen

doi:10.3390/pharmaceutics13111903

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−-emitter 177Lu was conjugated to DTPA-polyethylene glycol (PEG) decorated gold nanostars (177Lu-DTPA-pAuNS) used in surface-enhanced Raman scattering and photothermal therapy (PTT). The accumulation and therapeutic efficacy of 177Lu-DTPA-pAuNS were compared with those of 177Lu-DTPA on an orthotopic HNSCC tumor model. The SPECT/CT imaging and biodistribution studies showed that 177Lu-DTPA-pAuNS can be accumulated in the tumor up to 15 days, but 177Lu-DTPA could not be detected at 24 h after injection. The tumor viability and growth were suppressed by injected 177Lu-DTPA-pAuNS but not nonconjugated 177Lu-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 of 177Lu-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 of 177Lu-DTPA-pAuNS and PTT compared to 177Lu-DTPA-pAuNS alone. In conclusion, 177Lu-DTPA-pAuNS may be considered as a potential radiopharmaceutical agent for HNSCC brachytherapy.

Highlights

Licensee MDPI, Basel, Switzerland.Head and neck squamous cell carcinoma (HNSCC) ranks sixth in incidence around the world
The theranostic radionuclide 177 Lu was conjugated to the PEGylated AuNS
The radio TLC analysis showed that the labeling efficiency of 177 LuDTPA-PEGylated AuNS (pAuNS) was around 87%, and the EDTA challenge with excess EDTA did not significantly affect the labeling efficiency (Figure 1B)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) ranks sixth in incidence around the world. The 5-year survival rate of HNSCC is around 65% and locoregional recurrence is believed to be a major limitation of various treatments, including surgical and nonsurgical strategies [1,2]. Unlike other cancers that occur in parenchymal organs, the dissemination of HNSCC is mainly caused by local invasion instead of distant metastasis [3].

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Conclusion