2. Academic Validation
  3. [177Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy

[177Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy

  • Eur J Nucl Med Mol Imaging. 2023 Mar 6. doi: 10.1007/s00259-023-06155-x.
Qiaomiao Lu 1 2,  Yu Long 1 2,  Yongkang Gai 1 2 3,  Qingyao Liu 1 2 3,  Dawei Jiang 1 2 3,  Xiaoli Lan 4 5 6
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
  • 2 Hubei Key Laboratory of Molecular Imaging, Wuhan, Hubei, 430022, China.
  • 3 Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, 430022, China.
  • 4 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China. xiaoli_lan@hust.edu.cn.
  • 5 Hubei Key Laboratory of Molecular Imaging, Wuhan, Hubei, 430022, China. xiaoli_lan@hust.edu.cn.
  • 6 Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, 430022, China. xiaoli_lan@hust.edu.cn.
PMID: 36877233 DOI: 10.1007/s00259-023-06155-x
Abstract

Purpose: This study aimed to explore the feasibility of using [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 and [177Lu]Lu-Evans blue (EB)-PSMA-617 for in vivo radioligand therapy by single-dose administration in a PSMA-positive hepatocellular carcinoma (HCC) xenograft mouse model.

Methods: [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were prepared, and labelling efficiency and radiochemical purity were determined. A HepG2 human HCC subcutaneous xenograft mouse model was established. After intravenous injection of [177Lu]Lu-PSMA-617 or [177Lu]Lu-EB-PSMA-617 (37 MBq) into the mouse model, single-photon emission computed tomography/computed tomography (SPECT/CT) was performed. Biodistribution studies were conducted to verify targeting specificity and pharmacokinetics. In the radioligand therapy study, mice were randomized into 4 groups: 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, 7.4 MBq [177Lu]Lu-EB-PSMA-617, and saline (control). A single-dose administration was applied at the beginning of therapy studies. Tumor volume, body weight, and survival were monitored every 2 days. After the end of therapy, mice were euthanized. Tumors were then weighed, and systemic toxicity was evaluated via blood testing and histological examination of healthy organs.

Results: [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were successfully prepared with high purity and stability. SPECT/CT and biodistribution showed that tumor uptake was higher and persisted longer for [177Lu]Lu-EB-PSMA-617 compared with [177Lu]Lu-PSMA-617. [177Lu]Lu-PSMA-617 was rapidly cleared from the blood, while [177Lu]Lu-EB-PSMA-617 persisted for significantly longer. In radioligand therapy studies, tumor growth was significantly suppressed in the 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, and 7.4 MBq [177Lu]Lu-EB-PSMA-617 groups compared to the saline group. Median survival was 40, 44, 43, and 30 days, respectively. No healthy organ toxicity was observed in safety and tolerability evaluation.

Conclusions: Radioligand therapy using [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 significantly suppressed tumor growth and prolonged survival time in PSMA-positive HCC xenograft mice without obvious toxicity. These radioligands appear promising for clinical use in humans, and future studies are warranted.

Keywords

Hepatocellular carcinoma; Lutetium-177; Prostate-specific membrane antigen; Radioligand therapy; Tumor-associated endothelium.

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