PEGylated gold nanostars (pAuNSs) and their radioactive surrogate (¹¹¹In–DTPA–pAuNS), with unique physiochemical properties, are thought to be a promising agent for image-guided photothermal therapy (PTT).

Colorectal cancer is one of the major causes of cancer-related death in Taiwan and worldwide. Patients with peritoneal metastasis from colorectal cancer have reduced overall survival and poor prognosis. Hybrid protein-inorganic nanoparticle systems have displayed multifunctional applications in solid cancer theranostics. In this study, a gold nanocore-encapsulated human serum albumin nanoparticle (Au@HSANP), which is a hybrid protein-inorganic nanoparticle, and its radioactive surrogate ¹¹¹In-labeled Au@HSANP (¹¹¹In-Au@HSANP), were developed and their biological behaviors were investigated in a tumor/ascites mouse model. ¹¹¹In-Au@HSANP was injected either intravenously (iv) or intraperitoneally (ip) in CT-26 tumor/ascites-bearing mice. After ip injection, a remarkable and sustained radioactivity retention in the abdomen was noticed, based on microSPECT images. After iv injection, however, most of the radioactivity was accumulated in the mononuclear phagocyte system. The results of biodistribution indicated that ip administration was significantly more effective in increasing intraperitoneal concentration and tumor accumulation than iv administration. The ratios of area under the curve (AUC) of the ascites and tumors in the ip-injected group to those in the iv-injected group was 93 and 20, respectively. This study demonstrated that the ip injection route would be a better approach than iv injections for applying gold-albumin nanoparticle in peritoneal metastasis treatment.

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.

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of ¹³¹I-MIP-1145 to develop ¹³¹I-iodofluoropicolinamide benzamide (¹³¹I-IFPABZA) and ¹³¹I-iodofluoronicotiamide benzamide (¹³¹I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. ¹³¹I-IFPABZA (Log P = 2.01) was more lipophilic than ¹³¹I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with ¹³¹I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with ¹³¹I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of ¹³¹I-IFNABZA- and ¹³¹I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of ¹³¹I-IFNABZA with the melanin-targeted agents reported in the literature, ¹³¹I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using ¹³¹I-IFNABZA as a theranostic agent against melanoma.

Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (¹¹¹In/¹⁷⁷Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of ¹¹¹In/¹⁷⁷Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the ¹¹¹In/¹⁷⁷Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of ¹⁷⁷Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of ¹⁷⁷Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. ¹¹¹In/¹⁷⁷Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma.