SSTR2-targeted theranostics in hepatocellular carcinoma
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
While the clinical use of radiolabeled somatostatin analogs is established in neuroendocrine tumors, there is significant interest in expanding their use for other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC);
Methods
We measured SSTR2 expression in HCC cell lines and clinical samples using qRT-PCR, Western blot, and a public dataset. We evaluated [ 67 Gallium]Ga-DOTATATE uptake, tested [ 177 Lutetium]Lu-DOTATATE cytotoxicity, and assessed [ 68 Gallium]Ga-DOTATATE tumor targeting in HCC animal models and a patient via PET/CT;
Results
SSTR2 expression was confirmed in HCC cell lines and clinical samples. Radioligand uptake studies validated SSTR2-mediated [ 67 Gallium]Ga-DOTATATE uptake, and [ 177 Lutetium]Lu-DOTATATE treatment reduced cell proliferation. [ 68 Gallium]Ga-DOTATATE PET/CT scans detected tumors in animal models and spinal metastases in a patient with HCC;
Conclusion
These findings suggest for the first time that SSTR2-based theranostics could have strong implications for detection and treatment of HCC.
Simple Summary
This study investigates the use of SSTR2-targeted theranostics, combining diagnostic and therapeutic approaches, in hepatocellular carcinoma (HCC). We confirmed significant SSTR2 expression in HCC cells and patient samples, showing that radiolabeled compounds such as [ 67 Ga]Ga-DOTATATE and [ 177 Lu]Lu-DOTATATE, commonly used in neuroendocrine tumors, could also target HCC. In preclinical models and a patient case, PET/CT imaging and treatments demonstrated effective tumor detection and shrinkage. These findings suggest that SSTR2-targeted theranostics could offer a novel, targeted method for diagnosing and treating HCC, potentially improving outcomes for patients with this challenging cancer.
