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

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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.

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Availability of data and materials

The data that support the findings of this study are original and not obtained from any publications or elsewhere. Data are available from the corresponding author upon reasonable request.

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Funding

The research reported in this publication was supported by Mazandaran University of Medical Sciences under the grand 1432.

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Sajjad Molavipordanjani

  2. Molecular and Cell Biology Research Center (MCBRC), Hemoglobinopathy Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Tahoora Mousavi

  3. Department of Radiology, Faculty of Allied Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Alireza Khorramimoghaddam

  4. Department of Anatomy, Molecular and Cell Biology Research, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Fereshteh Talebpour Amiri

  5. Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Seyed Mohammad Abedi

  6. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Seyed Jalal Hosseinimehr

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  1. Sajjad Molavipordanjani
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Contributions

SJH designed and supervised the study, carried out data analysis and drafted the manuscript; SM carried out data collection and data analysis and drafted the manuscript. TM, AK and FT carried out data collection and data analysis. SMA participated in data collection. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Seyed Jalal Hosseinimehr.

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The animal study was approved by the Mazandaran University of Medical Sciences (ID #IR.MAZUMS.REC.1397.1432).

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Molavipordanjani, S., Mousavi, T., Khorramimoghaddam, A. et al. The preclinical study of 177Lu-DOTA-LTVSPWY as a potential therapeutic agent against HER2 overexpressed cancer. Ann Nucl Med 37, 400–409 (2023). https://doi.org/10.1007/s12149-023-01839-8

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  • DOI: https://doi.org/10.1007/s12149-023-01839-8

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