Technetium-99m Tricarbonyl Pyridylpiperazine Radiotracers Targeting 5-HT₇ Receptors for SPECT Imaging of Glioblastoma

Briones-Aranda A, Flores-Durán D, Romero-Nava R, Corzo-Gómez JC, Cruz-Trujillo R, Toalá-Sepúlveda F, et al. Role of 5-HT1A and 5-HT7 receptors in memory regulation and the importance of their coexpression: a systematic review. Biomolecules. 2025;15:762.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Wang N, Zhang L, Zhuang Y, Xin Q, Gu X, et al. Serotonin (5-Hydroxytryptamine): metabolism, signaling, biological functions, diseases, and emerging therapeutic opportunities. MedComm. 2020;2025(6):e70383.

Google Scholar 

Liu S, He M, Sun H, Wu Y, Jin W. 5-Hydroxytryptamine G-protein-coupled receptor family genes: key players in cancer prognosis, immune regulation, and therapeutic response. Genes (Basel). 2024;15:1541-62.

Wang X, Shi M, Tian J, Yu W. Cancer and neurotransmitter receptors. Chin Med J. 2025;138(13):1540–58.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meleiro M, Henrique R. Epigenetic alterations in glioblastoma multiforme as novel therapeutic targets: a scoping review. Int J Mol Sci. 2025;26.

Singh S, Dey D, Barik D, Mohapatra I, Kim S, Sharma M, et al. Glioblastoma at the crossroads: current understanding and future therapeutic horizons. Signal Transduct Target Ther. 2025;10:213.

Article  PubMed  PubMed Central  Google Scholar 

Liu Y, Zhou F, Ali H, Lathia JD, Chen P. Immunotherapy for glioblastoma: current state, challenges, and future perspectives. Cell Mol Immunol. 2024;21:1354–75.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stockham AL, Tievsky AL, Koyfman SA, Reddy CA, Suh JH, Vogelbaum MA, et al. Conventional MRI does not reliably distinguish radiation necrosis from tumor recurrence after stereotactic radiosurgery. J Neurooncol. 2012;109:149–58.

Article  PubMed  Google Scholar 

Lawrence LSP, Chan RW, Singnurkar A, Detsky J, Heyn C, Maralani PJ, et al. Applications of advanced imaging for radiotherapy planning and response assessment in the central nervous system. Tomography. 2025;11:68.

Article  PubMed  PubMed Central  Google Scholar 

Binneboese A, Covington MF, Horn KP, Archibald ZG, Boucher KM, Morton KA, et al. Correlation between FDG-PET uptake and survival in patients with primary brain tumors. Am J Nucl Med Mol Imaging. 2021;11:196–206.

CAS  PubMed  PubMed Central  Google Scholar 

Cao X, Tan D, Liu Z, Liao M, Kan Y, Yao R, et al. Differentiating solitary brain metastases from glioblastoma by radiomics features derived from MRI and 18F-FDG-PET and the combined application of multiple models. Sci Rep. 2022;12:5722.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kawasaki T, Miwa K, Shinoda J, Asano Y, Takei H, Ikegame Y, et al. Dissociation between 11 C-methionine-positron emission tomography and gadolinium-enhanced magnetic resonance imaging in longitudinal features of glioblastoma after postoperative radiotherapy. World Neurosurg. 2019;125:93–100.

Article  PubMed  Google Scholar 

Palanichamy K, Chakravarti A. Diagnostic and prognostic significance of methionine uptake and methionine positron emission tomography imaging in gliomas. Front Oncol. 2017;7:257.

Article  PubMed  PubMed Central  Google Scholar 

Pessina F, Navarria P, Clerici E, Bellu L, Franzini A, Milani D et al. Role of 11 C Methionine Positron Emission Tomography (11CMETPET) for surgery and radiation therapy planning in newly diagnosed glioblastoma patients enrolled into a phase II clinical study. J Clin Med. 2021;10:2313-26.

Sipos D, Debreczeni-Máté Z, Ritter Z, Freihat O, Simon M, Kovács Á. Complex diagnostic challenges in glioblastoma: the role of (18)F-FDOPA PET imaging. Pharmaceuticals (Basel). 2024;17:1215-31.

Sipos D, László Z, Tóth Z, Kovács P, Tollár J, Gulybán A, et al. Additional value of 18F-FDOPA amino acid analog radiotracer to irradiation planning process of patients with glioblastoma multiforme. Front Oncol. 2021;11:699360.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferjančič P, Ebert MA, Francis R, Nowak AK, Jeraj R. Repeatability of Quantitative 18F-FET PET in Glioblastoma. Biomed Phys Eng Express. 2021;7:035020.

Nedergaard MK, Michaelsen SR, Urup T, Broholm H, El Ali H, Poulsen HS, et al. 18F-FET microPET and microMRI for anti-VEGF and anti-PlGF response assessment in an orthotopic murine model of human glioblastoma. PLoS ONE. 2015;10:e0115315.

Article  PubMed  PubMed Central  Google Scholar 

Dagher SA, Johnson JM, Mohamed RMM, Ansari S, Mawlawi O, Liu HL, et al. Study of 18 F-fluciclovine PET for serial assessment of glioblastoma tumor volumes during surgery and radiotherapy. J Neurooncol. 2025;175:549–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bolcaen J, Kleynhans J, Nair S, Verhoeven J, Goethals I, Sathekge M, et al. A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma. Theranostics. 2021;11:7911–47.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alexiou GA, Tsiouris S, Kyritsis AP, Fotakopoulos G, Goussia A, Voulgaris S, et al. The value of 99mTc-tetrofosmin brain SPECT in predicting survival in patients with glioblastoma multiforme. J Nucl Med. 2010;51:1923–6.

Article  PubMed  Google Scholar 

Osawa S, Tosaka M, Horiguchi K, Tokue A, Higuchi T, Tsushima Y, et al. Usefulness of dual isotope (123)I-IMP and (201)Tl SPECT for the diagnosis of primary central nervous system lymphoma and glioblastoma. Int J Clin Oncol. 2022;27:1264–72.

Article  CAS  PubMed  Google Scholar 

Hulshof MC, Rehmann CJ, Booij J, van Royen EA, Bosch DA, González González D. Lack of perfusion enhancement after administration of nicotinamide and carbogen in patients with glioblastoma: a 99mTc-HMPAO SPECT study. Radiother Oncol. 1998;48:135–42.

Article  CAS  PubMed  Google Scholar 

Nagamachi S, Jinnouchi S, Nabeshima K, Nishii R, Flores L 2nd, Kodama T, et al. The correlation between 99mTc-MIBI uptake and MIB-1 as a nuclear proliferation marker in glioma–a comparative study with 201Tl. Neuroradiology. 2001;43:1023–30.

Article  CAS  PubMed  Google Scholar 

Saednia S, Emami S, Molavipordanjani S, Abedi SM, Amiri FT, Hosseinimehr SJ. Synthesis and biological evaluation of (99m)Tc-labeled phenylpiperazine derivatives as selective serotonin-7 receptor ligands for brain tumor imaging. Mol Pharm. 2021;18:2360–74.

Article  CAS  PubMed  Google Scholar 

Karimi M, Mardanshahi A, Irannejad H, Mohammad Abedi S, Molavipordanjani S. Synthesis and evaluation of (99m)Tc-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5HT(7) receptors. Bioorg Chem. 2023;135:106486.

Article  CAS  PubMed  Google Scholar 

Mardanshahi A, Vaseghi S, Hosseinimehr SJ, Abedi SM, Molavipordanjani S. 99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors. Ann Nucl Med. 2024;38:139–53.

Article  CAS  PubMed  Google Scholar 

Molavipordanjani S. 99mTc(CO)3-Labeled 1-(3-Nitropyridin-2-yl) Piperazine as potential radioligand for 5-HT7 receptors. J Mazandaran Univ Med Sci. 2024;34:14–25.

Google Scholar 

Lacivita E, Niso M, Hansen HD, Di Pilato P, Herth MM, Lehel S, et al. Design, synthesis, radiolabeling and in vivo evaluation of potential positron emission tomography (PET) radioligands for brain imaging of the 5-HT7 receptor. Bioorg Med Chem. 2014;22:1736–50.

Article  CAS  PubMed  Google Scholar 

Narayanaswami V, Tong J, Fiorino F, Severino B, Sparaco R, Magli E, et al. Synthesis, in vitro and in vivo evaluation of 11 C-O-methylated arylpiperazines as potential serotonin 1A (5-HT1A) receptor antagonist radiotracers. EJNMMI Radiopharm Chem. 2020;5:13.

Article  PubMed  PubMed Central  Google Scholar 

Hazari PP, Pandey A, Chaturvedi S, Mishra AK. New trends and current status of positron-emission tomography and single-photon-emission computerized tomography radioligands for neuronal serotonin receptors and serotonin transporter. Bioconjug Chem. 2017;28:2647–72.

Article  CAS  PubMed  Google Scholar 

Zenati K, Malek Saied N, Asmi A, Saidi M. Synthesis and biological evaluation of 99mTc labeled aryl piperazine derivatives as cerebral radiotracers. J Radioanal Nucl Chem. 2017;312:67–74.

Article  CAS  Google Scholar 

Shimoda Y, Yui J, Xie L, Fujinaga M, Yamasaki T, Ogawa M, et al. Synthesis and evaluation of 1-[2-(4-[11 C]methoxyphenyl)phenyl]piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain. Bioorg Med Chem. 2013;21:5316–22.

Article  CAS  PubMed  Google Scholar 

Alberto R, Ortner K, Wheatley N, Schibli R, Schubiger AP. Synthesis and properties of boranocarbonate: a convenient in situ CO source for the aqueous preparation of [(99m)Tc(OH(2))3(CO)3]+. J Am Chem Soc. 2001;123:3135–6.

Article  CAS  PubMed 

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