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Pharmaceuticals
Volume 18
Issue 8
10.3390/ph18081175
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Development of AGT-7: An Innovative 99mTc-Labeled Theranostic Platform for Glioblastoma Imaging and Therapy

by
Stavroula G. Kyrkou
1,
Vasileios-Panagiotis Bistas
1,
Evangelia-Alexandra Salvanou
2,
Timothy Crook
3,
Maria Giannakopoulou
4,
Vasiliki Zoi
4,
Maximos Leonardos
5,
Andreas Fotopoulos
4,
Chrissa Sioka
4,
Ioannis Leonardos
5,
George A. Alexiou
4,
Penelope Bouziotis
2,* and
Andreas G. Tzakos
1,*
1
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
2
Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, Greece
3
John Fulcher Neuro-Oncology Laboratory, Department of Brain Sciences, Division of Neuroscience, Faculty of Medicine, Imperial College London, London W12 0NN, UK
4
Neurosurgical Institute, School of Medicine, University of Ioannina, 45500 Ioannina, Greece
5
Laboratory of Zoology, Department of Biological Applications and Technologies, University of Ioannina, 45110 Ioannina, Greece
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(8), 1175; https://doi.org/10.3390/ph18081175
Submission received: 4 July 2025 / Revised: 28 July 2025 / Accepted: 5 August 2025 / Published: 8 August 2025
(This article belongs to the Special Issue Development of Novel Radiopharmaceuticals for SPECT and PET Imaging)
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Abstract

Background: Glioblastoma, the most common malignant primary brain tumor in adults, continues to present a major therapeutic challenge, with a median survival of only 12–15 months and a 5-year survival rate below 2%. Despite aggressive treatment—including maximal surgical excision, radiation, and temozolomide (TMZ) chemotherapy—recurrent disease is nearly universal due to the tumor’s infiltrative nature. Objectives: To address the critical need for improved diagnostic and therapeutic strategies for glioblastoma multiforme (GBM), we have developed an innovative theranostic molecule, [⁹⁹ᵐTc]Tc-AGT-7. Methods: AGT-7 integrates diagnostic and therapeutic modalities comprising [99mTc]Tc-TF (a nuclear medicine imaging agent) and TMZ. The diagnostic component has been tailored to selectively accumulate in glioma mitochondria. A chelating moiety enables radiolabeling with technetium-99m (⁹⁹ᵐTc) for precise Single-Photon Emission Computed Tomography (SPECT) imaging. The therapeutic arm includes the tethering of a TMZ moiety for localized cytotoxicity. Conclusions: In vitro studies illustrated that AGT-7 has potent cytotoxic effects in GBM cell lines (T98 and U87), with greater efficacy than TMZ, and toxicity assays in zebrafish embryos indicated a favorable safety profile. Biodistribution studies in CFW mice demonstrated that [⁹⁹ᵐTc]Tc-AGT-7 exhibited a ~10-fold lower heart uptake compared to [⁹⁹ᵐTc]Tc-TF, implying reduced off-target cardiac localization. This significantly lowers the risk of cardiotoxicity and enhances AGT-7’s potential as a glioma-targeted theranostic agent.
Keywords: glioblastoma; Tetrofosmin; temozolamide; theranostics; technetium-99m molecular imaging; SPECT; radiopharmaceuticals glioblastoma; Tetrofosmin; temozolamide; theranostics; technetium-99m molecular imaging; SPECT; radiopharmaceuticals
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MDPI and ACS Style

Kyrkou, S.G.; Bistas, V.-P.; Salvanou, E.-A.; Crook, T.; Giannakopoulou, M.; Zoi, V.; Leonardos, M.; Fotopoulos, A.; Sioka, C.; Leonardos, I.; et al. Development of AGT-7: An Innovative 99mTc-Labeled Theranostic Platform for Glioblastoma Imaging and Therapy. Pharmaceuticals 2025, 18, 1175. https://doi.org/10.3390/ph18081175

AMA Style

Kyrkou SG, Bistas V-P, Salvanou E-A, Crook T, Giannakopoulou M, Zoi V, Leonardos M, Fotopoulos A, Sioka C, Leonardos I, et al. Development of AGT-7: An Innovative 99mTc-Labeled Theranostic Platform for Glioblastoma Imaging and Therapy. Pharmaceuticals. 2025; 18(8):1175. https://doi.org/10.3390/ph18081175

Chicago/Turabian Style

Kyrkou, Stavroula G., Vasileios-Panagiotis Bistas, Evangelia-Alexandra Salvanou, Timothy Crook, Maria Giannakopoulou, Vasiliki Zoi, Maximos Leonardos, Andreas Fotopoulos, Chrissa Sioka, Ioannis Leonardos, and et al. 2025. "Development of AGT-7: An Innovative 99mTc-Labeled Theranostic Platform for Glioblastoma Imaging and Therapy" Pharmaceuticals 18, no. 8: 1175. https://doi.org/10.3390/ph18081175

APA Style

Kyrkou, S. G., Bistas, V.-P., Salvanou, E.-A., Crook, T., Giannakopoulou, M., Zoi, V., Leonardos, M., Fotopoulos, A., Sioka, C., Leonardos, I., Alexiou, G. A., Bouziotis, P., & Tzakos, A. G. (2025). Development of AGT-7: An Innovative 99mTc-Labeled Theranostic Platform for Glioblastoma Imaging and Therapy. Pharmaceuticals, 18(8), 1175. https://doi.org/10.3390/ph18081175

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