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[99mTc]-labeling and evaluation of a new linear peptide for imaging of glioblastoma as a αvβ3-positive tumor

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A Correction to this article was published on 12 October 2022

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Abstract

Purpose

In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a αvβ3-positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides.

Procedures.

One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N′-diacetic acid (EDDA) as co-ligand system. Then, this 99mTc-labeled peptide ([99mTc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (Kd). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a αvβ3-positive tumor.

Results

The radiochemical yield of [99mTc]Tc-M-7 was obtained ˃95%. This 99mTc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this 99mTc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The Kd value for [99mTc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were αvβ3-mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this 99mTc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides, [99mTc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80).

Conclusions

This small linear 99mTc-labeled peptide, with high affinity to αvβ3 integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [99mTc]Tc-M-7 can be of service to as a new candidate for early detection of αvβ3-positive tumors.

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Acknowledgements

This work was the subject part of the thesis of Sajad Kaihani as a PhD student of the Mazandaran University of Medical Sciences and was supported with grant number 6301.

Funding

This study was supported by Mazandaran University of Medical Sciences, 6301, Nourollah Sadeghzadeh.

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Authors and Affiliations

  1. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, 48471-93698, Mazandaran, Iran

    Sajad Kaihani & Nourollah Sadeghzadeh

  2. Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Sajad Kaihani

  3. Immunogenetics Research Centre, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Saeid Abediankenari

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

    Seyed Mohammad Abedi

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  1. Sajad Kaihani
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  2. Nourollah Sadeghzadeh
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  3. Saeid Abediankenari
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  4. Seyed Mohammad Abedi
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Correspondence to Nourollah Sadeghzadeh.

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Kaihani, S., Sadeghzadeh, N., Abediankenari, S. et al. [99mTc]-labeling and evaluation of a new linear peptide for imaging of glioblastoma as a αvβ3-positive tumor. Ann Nucl Med 36, 976–985 (2022). https://doi.org/10.1007/s12149-022-01786-w

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