SSTR2-Targeted Theranostics in Hepatocellular Carcinoma.

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Therapy

Background:

• Radiolabeled somatostatin analogs are established for neuroendocrine tumors.
• There is increasing interest in SSTR2-targeted agents for other cancers.
• This study explores SSTR2 theranostics in hepatocellular carcinoma (HCC).

Purpose of the Study:

• To evaluate the expression of somatostatin receptor 2 (SSTR2) in hepatocellular carcinoma (HCC).
• To assess the diagnostic and therapeutic potential of SSTR2-targeted radiopharmaceuticals in HCC.
• To investigate the combination of SSTR2-targeted therapy with sorafenib in HCC.

Main Methods:

• SSTR2 expression was analyzed in HCC cell lines and clinical samples using qRT-PCR, Western blot, and public data.
• Radioligand uptake (⁶⁷Ga-DOTATATE), cytotoxicity (¹⁷⁷Lu-DOTATATE), and tumor targeting (⁶⁸Ga-DOTATATE PET/CT) were evaluated.
• Animal models and a patient with HCC were used for in vivo imaging and therapeutic assessment.

Main Results:

• SSTR2 expression was confirmed in HCC cell lines and patient samples.
• ⁶⁷Ga-DOTATATE showed SSTR2-mediated uptake in HCC.
• ¹⁷⁷Lu-DOTATATE reduced HCC cell proliferation and enhanced sorafenib's anti-tumor effect.
• ⁶⁸Ga-DOTATATE PET/CT successfully identified HCC tumors and metastases.

Conclusions:

• SSTR2-based theranostics demonstrate significant potential for HCC detection and treatment.
• These findings support the clinical utility of SSTR2-targeted agents in managing hepatocellular carcinoma.