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177Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers

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Abstract

Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of β- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of 177LuCl3 (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of 177Lu-MGCL2 and 177Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of 177Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.

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Acknowledgements

The authors are highly grateful to Prof. Dr. Stephen John Mather for his countless assistance in this study and Higher Education Commission (HEC), Islamabad, Pakistan for funding (Project No. 3413/NRPU/HEC/R&D/14/702). The authors are also thankful to the Dr. Jawad Akhtar Hussain Gillani (Nuclear Oncologist), Institute of Nuclear Medicine Oncology and Radiotherapy (INOR), Abbottabad for providing platform for labeling and SPECT scintigraphy study.

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Authors and Affiliations

  1. Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan

    Syed Faheem Askari Rizvi, Syed Ali Raza Naqvi & Rashid Rasheed

  2. Pakistan Institute of Nuclear Science and Technology (PINSTECH), Nilore, Islamabad, Pakistan

    Samina Roohi

  3. Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan

    Tauqir A. Sherazi

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  1. Syed Faheem Askari Rizvi
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  2. Syed Ali Raza Naqvi
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  3. Samina Roohi
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  4. Tauqir A. Sherazi
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  5. Rashid Rasheed
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Correspondence to Syed Ali Raza Naqvi or Tauqir A. Sherazi.

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Rizvi, S.F.A., Naqvi, S.A.R., Roohi, S. et al. 177Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers. Mol Biol Rep 45, 1759–1767 (2018). https://doi.org/10.1007/s11033-018-4319-0

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  • DOI: https://doi.org/10.1007/s11033-018-4319-0

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