The preclinical study of 177Lu-DOTA-LTVSPWY as a potential therapeutic agent against HER2 overexpressed cancer

  • Ann Nucl Med. 2023 Jul;37(7):400-409. doi: 10.1007/s12149-023-01839-8.
Sajjad Molavipordanjani  1 ,  Tahoora Mousavi  2 ,  Alireza Khorramimoghaddam  3 ,  Fereshteh Talebpour Amiri  4 ,  Seyed Mohammad Abedi  5 ,  Seyed Jalal Hosseinimehr  6
Affiliations
  • 1. Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
  • 2. Molecular and Cell Biology Research Center (MCBRC), Hemoglobinopathy Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 3. Department of Radiology, Faculty of Allied Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 4. Department of Anatomy, Molecular and Cell Biology Research, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 5. Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 6. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. [email protected].
PMID: 37115407 DOI: 10.1007/s12149-023-01839-8
Abstract

Background: Peptide receptor radionuclide therapy (PRRT) has evolved in Cancer therapy and diagnosis. LTVSPWY, as a peptide, can target HER2 receptor; on the Other hand, 177Lu emits β- which is helpful for Cancer therapy. The radiolabeling of LTVSPWY with 177Lu results in a therapeutic agent (177Lu-DOTA-LTVSPWY) capable of Cancer treatment.

Methods: 177Lu-DOTA-LTVSPWY was prepared with high radiochemical purity (RCP). The stability was investigated in saline and human serum. The radiotracer affinity toward the SKOV-3 cell line with overexpression of the HER2 receptor was evaluated. Then the impact of the radiotracer on the colony formation of the SKOV-3 cell line was investigated with colony assay. Moreover, the biodistribution of this radiotracer in SKOV-3 xenograft tumor-bearing nude mice were also studied to determine the radiotracer accumulation in the tumor site. The mice were treated with 177Lu-DOTA-LTVSPWY and subjected to histopathological evaluation.

Results: The RCP of 177Lu-DOTA-LTVSPWY after radiolabeling and stability tests was more than 97.7%. The radiotracer displayed high affinity toward the SKOV-3 cell line (KD = 6.6 ± 3.2 nM). Treatment of the SKOV-3 cell line with the radiotracer reduces the SKOV-3 colony survival to less than 3% for 5 MBq of the radiotracer. Tumor-to-muscle (T/M) ratio is the highest at 48 h and 1 h post-injection (2.3 and 4.75, respectively). The histopathological study also confirms the cellular damage to the tumor tissue.

Conclusions: 177Lu-DOTA-LTVSPWY can recognize HER2 receptors in vivo and in vitro; hence, it can serve as a therapeutic agent.

Keywords
177Lu; HER2; LTVSPWY; PRRT; Radiolabeled peptide; Therapy.
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