Brachytherapy Approach Using 177Lu 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−-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.

Novel Implications of Nanoparticle-Enhanced Radiotherapy and Brachytherapy: Z-Effect and Tumor Hypoxia

“…The multi-measured biodistribution profiles of 177 Lu-labelled nanoparticles also demonstrate a remarkably higher uptake of these nanoparticles into the tumor tissues and low accumulation in other organs [ 102 ]. As we discussed above, Lin M. et al conjugated the β-emitter 177 Lu to DTPA-polyethylene glycol (PEG) decorated gold nanostars ( 177 Lu-DTPA-pAuNS) and explored it as a potential radiopharmaceutical agent for head and neck squamous cell carcinoma (HNSCC) [ 39 ]. The in vivo and in vitro accumulation, therapeutic efficacy and the enhancement effects of 177 Lu-DTPA-pAuNS were compared and verified on orthotopic HNSCC tumor models and cell lines, respectively.…”

“…The in vivo and in vitro accumulation, therapeutic efficacy and the enhancement effects of 177 Lu-DTPA-pAuNS were compared and verified on orthotopic HNSCC tumor models and cell lines, respectively. The survival rates among different treatments were also compared using the Kaplan–Meier method [ 39 ].…”

“…Furthermore, the radiolabeled 177 Lu-T-AuNP impregnated with panitumumab can impair the EGFR(+) triple negative breast cancers [ 38 ]. Tumor-suppressive effects are typically higher with radiolabeled 177 Lu-DTPA-pAuNS in combination with photothermal therapy than the individual therapy of 177 Lu-DTPA-pAuNS in head and neck squamous cell carcinoma [ 39 ]. Another study described the efficacy of ‘PAMAM-G4–( 177 Lu–dendrimer)–bombesin–folate’ for targeting gastrin-releasing peptide receptors as well as folate receptors in lung cancer cells [ 40 ].…”

Progress of Nanomaterials-Based Photothermal Therapy for Oral Squamous Cell Carcinoma

“…Moreover, compared with 177 Lu-DTPA-pAuNS alone, the combination of 177 Lu-DTPA-pAuNS and PTT (793 nm, 1 W/cm 2 , 6 min) can further enhance the tumor inhibition effect. Therefore, 177 Lu-DTPA-pAuNS has great application prospects in the field of synergistic therapy of brachytherapy and PTT ( Figure 2 C,D) [ 41 ]. In addition, Sasidharan et al revealed that gold nanostars have good computed tomography contrast characteristics and obvious photothermal cytotoxicity to oral epithelial cancer cells [ 64 ].…”

“…( D ) TEM images of pAuNS and 177 Lu-DTPA-pAuNS. Adapted with permission from [ 39 , 40 , 41 ]. Copyright 2022, Elsevier, Elsevier and Multidisciplinary Digital Publishing Institute, respectively.…”