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

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 (K_D = 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.