Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Preparation of 64Cu-NODAGA-RGD-BBN labeled compound and its absorbed dose estimation in humans based on mouse data

Document Type : Research Paper

Authors

N. Amraee 1
B. Alirezapour 2
M. Hosntalab 1
A. Haddadi 1
H. Yousefnia 2

1 Medical Radiation Engineering Department, Science and Research Branch, Islamic Azad University, P.O. Box: 14515-775, Tehran-Iran

2 Radiation Application Research School, Nuclear Science and Technology Research Institute, P.O.BOX: 14893-836, Tehran- Iran

https://doi.org/10.24200/nst.2023.1225.1800
Abstract
Calculating the absorbed dose in the human body is one of the first steps in radiopharmaceutical development. This study estimates the dose absorbed by humans from the novel identified compound of 64Cu-NODAGA-RGD-BBN. For this purpose, 64Cu-NODAGA-RGD-BBN labeled compound was first prepared by changing the labeling decisions in optimal conditions. The stability of labeled heterodimer peptide was evaluated in phosphate-buffered saline (PBS) and human blood serum for 12 hours. After that, the complex's bio-distribution was investigated in tumor-bearing mice for 12 hours after injection. Finally, the dose absorbed by humans after injection of the 64Cu-NODAGA-RGD-BBN labeled compound was calculated based on mouse data using RADAR and mass extrapolation methods. The results showed that the obtained labeled compound could be produced with a high radiochemical purity of more than 99% and is highly stable (higher than 96%). 64Cu-NODAGA-RGD-BBN showed high uptake in gastrin-releasing peptide receptor-expressing tumors compared to other non-target organs. Furthermore, the dose assessment for this compound indicated that the body and other organs did not absorb a significant dose after injection.

Highlights

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  1. S.R. Nagalla, et al, There Are Three Distinct Forms of Bombesin: Identification of [Leu13] Bombesin, [Phe13] Bombesin, and [Ser3, Arg10, Phe13] Bombesin in the Frog Bombina Orientalis, J. Biol. Chem., 271, 7731-7737 (1996).

 

  1. T. Tonini, R. Francesca, P.C. Pier, Molecular basis of angiogenesis and cancer, Oncogene, 22, 6549-6556 (2003).

 

  1. D. Hanahan, A.W. Robert, Hallmarks of cancer: the next generation, Cell, 144, 646-674 (2011).

 

  1. R. Axelsson, et al, An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αv β 3-selective angiogenesis imaging agent 99mTc-NC100692, Acta Radiologica, 51, 40-46 (2010).

 

  1. L. Liu, et al, 99mTc-3PRGD2 scintimammography in palpable and nonpalpable breast lesions, Mol Imaging, 13, 7290-2014 (2014).

 

  1. M.E. Shinderman, et al, The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation, Oncogene, 35, 1977-1987 (2016).

 

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  1. M.L. Thakur, et al., Radiolabeled somatostatin analogs in prostate cancer, Nucl. Med. Biol., 24, 105-113 (1997).

 

  1. H. Yang, et al., Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide, EJNMMI Radiopharm Chem., 6, 1-16 (2021).

 

  1. E. Lopci, et al., Prognostic evaluation of disease outcome in solid tumors investigated with 64Cu-ATSM PET/CT, Clin. Nucl. Med., 41, e87-e92 (2016).

 

  1. I. Grassi, et al., Usefulness of 64Cu-ATSM in head and neck cancer: a preliminary prospective study, Clin. Nucl. Med., 39, e59-e63 (2014).

 

  1. S. Sasada, et al., 64Cu-DOTATrastuzumab PET imaging forHER2-specific primary lesions of breast cancer, Ann. Oncol., 28, 2028-2029 (2017).

 

  1. J.E. Mortimer, et al., Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64) Cu-DOTA-trastuzumab PET, J. Nucl. Med., 55, 23-29 (2014).

 

  1. A. Niccoli Asabella, et al., The copper radioisotopes: a systematic review with special interest to 64Cu, Biomed Res Int., 2014, 786463 (2014).

 

  1. M.G. Stabin, et al., Radiation dosimetry in nuclear medicine, Appl Radiat Isot, 50, 73-87 (1999).

 

  1. M.G. Stabin, et al., Physical models and dose factors for use in internal dose assessment, Health Phys., 85, 294‑310 (2003).

 

  1. H. Yousefnia, et al., Preliminary dosimetric evaluation of 166Ho-TTHMP for human based on biodistribution data in rats, Appl Rad Iso, 94, 260-265 (2014).

 

  1. R. Sparks, et al., Comparison of the Effectiveness of Some Common Animal Data Scaling Techniques In Estimating Human Radiation Dose, TN (United States): Oak Ridge Associated Universities. (1999).

 

  1. H. Yousefnia, et al, Preliminary dosimetric evaluation of (166) Ho‑TTHMP for human based on biodistribution data in rats, Appl Radiat Isot., 94, 260‑265 (2014).

 

  1. S. Shanehsazzadeh, et al., Estimated human absorbed dose for (68) Ga‑ECC based on mice data: Comparison with (67) Ga‑ECC, Ann Nucl Med., 29, 475‑481 (2015).

 

  1. M.G. Stabin, et al., OLINDA/EXM: The second‑generation personal computer software for internal dose assessment in nuclear medicine, J. Nucl. Med., 46, 1023-1027 (2005).

 

  1. D.J. Brenner, et al., Effective dose: A flawed concept that could and should be replaced, Br. J. Radiol., 81, 521‑523 (2008).

 

  1. Z. Liu, et al., 18F, 64Cu, and 68Ga Labeled RGD-Bombesin Heterodimeric Peptides for PET Imaging of Breast Cancer, Bioconjugate Chem., 20, 1016–1025 (2009).

 

  1. Z. Liu, et al., 68Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging, Europ. J. Nucl. Med. Mol. Imaging, 36, 1483-1494 (2009).

 

  1. Z. Liu, et al., Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FBPEG3-Glu-RGD-BBN, J. Med. Chem., 52, 425–432 (2009).

 

  1. N. Amraee, et al., Human dose assessment of 68Ga-NODAGA-RGD-BBN heterodimer peptide based on animal data, J. Med. Phys, 47, 287-293 (2022)

Keywords

RGD
Bombesin
Heterodimer peptide
Copper-64
Absorbed dose
  1. www.euro.who.int- World health organization, regional office for Europe.

 

  1. J. Ferlay, et al, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int J Cancer, 127, 2893-2917 (2010).

 

  1. R. Fischer, et al, Effects of psychodysleptic drug psilocybin on visual perception: Changes in brightness perference, Experientia, 25, 166-169 (1969).

 

  1. S.R. Nagalla, et al, There Are Three Distinct Forms of Bombesin: Identification of [Leu13] Bombesin, [Phe13] Bombesin, and [Ser3, Arg10, Phe13] Bombesin in the Frog Bombina Orientalis, J. Biol. Chem., 271, 7731-7737 (1996).

 

  1. T. Tonini, R. Francesca, P.C. Pier, Molecular basis of angiogenesis and cancer, Oncogene, 22, 6549-6556 (2003).

 

  1. D. Hanahan, A.W. Robert, Hallmarks of cancer: the next generation, Cell, 144, 646-674 (2011).

 

  1. R. Axelsson, et al, An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αv β 3-selective angiogenesis imaging agent 99mTc-NC100692, Acta Radiologica, 51, 40-46 (2010).

 

  1. L. Liu, et al, 99mTc-3PRGD2 scintimammography in palpable and nonpalpable breast lesions, Mol Imaging, 13, 7290-2014 (2014).

 

  1. M.E. Shinderman, et al, The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation, Oncogene, 35, 1977-1987 (2016).

 

  1. R. Huang, K.R. Einar, Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma, J. Exper. Clin. Cancer Res, 37, 1-14 (2018).

 

  1. T.W. Moody, et al, Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy, Frontiers in Endocrinology, 12, (2021).

 

  1. P. Moreno, et al, Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment, Expert Opinion on Therapeutic Targets, 20, 1055-1073 (2016).

 

  1. M.L. Thakur, et al., Radiolabeled somatostatin analogs in prostate cancer, Nucl. Med. Biol., 24, 105-113 (1997).

 

  1. H. Yang, et al., Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide, EJNMMI Radiopharm Chem., 6, 1-16 (2021).

 

  1. E. Lopci, et al., Prognostic evaluation of disease outcome in solid tumors investigated with 64Cu-ATSM PET/CT, Clin. Nucl. Med., 41, e87-e92 (2016).

 

  1. I. Grassi, et al., Usefulness of 64Cu-ATSM in head and neck cancer: a preliminary prospective study, Clin. Nucl. Med., 39, e59-e63 (2014).

 

  1. S. Sasada, et al., 64Cu-DOTATrastuzumab PET imaging forHER2-specific primary lesions of breast cancer, Ann. Oncol., 28, 2028-2029 (2017).

 

  1. J.E. Mortimer, et al., Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64) Cu-DOTA-trastuzumab PET, J. Nucl. Med., 55, 23-29 (2014).

 

  1. A. Niccoli Asabella, et al., The copper radioisotopes: a systematic review with special interest to 64Cu, Biomed Res Int., 2014, 786463 (2014).

 

  1. M.G. Stabin, et al., Radiation dosimetry in nuclear medicine, Appl Radiat Isot, 50, 73-87 (1999).

 

  1. M.G. Stabin, et al., Physical models and dose factors for use in internal dose assessment, Health Phys., 85, 294‑310 (2003).

 

  1. H. Yousefnia, et al., Preliminary dosimetric evaluation of 166Ho-TTHMP for human based on biodistribution data in rats, Appl Rad Iso, 94, 260-265 (2014).

 

  1. R. Sparks, et al., Comparison of the Effectiveness of Some Common Animal Data Scaling Techniques In Estimating Human Radiation Dose, TN (United States): Oak Ridge Associated Universities. (1999).

 

  1. H. Yousefnia, et al, Preliminary dosimetric evaluation of (166) Ho‑TTHMP for human based on biodistribution data in rats, Appl Radiat Isot., 94, 260‑265 (2014).

 

  1. S. Shanehsazzadeh, et al., Estimated human absorbed dose for (68) Ga‑ECC based on mice data: Comparison with (67) Ga‑ECC, Ann Nucl Med., 29, 475‑481 (2015).

 

  1. M.G. Stabin, et al., OLINDA/EXM: The second‑generation personal computer software for internal dose assessment in nuclear medicine, J. Nucl. Med., 46, 1023-1027 (2005).

 

  1. D.J. Brenner, et al., Effective dose: A flawed concept that could and should be replaced, Br. J. Radiol., 81, 521‑523 (2008).

 

  1. Z. Liu, et al., 18F, 64Cu, and 68Ga Labeled RGD-Bombesin Heterodimeric Peptides for PET Imaging of Breast Cancer, Bioconjugate Chem., 20, 1016–1025 (2009).

 

  1. Z. Liu, et al., 68Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging, Europ. J. Nucl. Med. Mol. Imaging, 36, 1483-1494 (2009).

 

  1. Z. Liu, et al., Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FBPEG3-Glu-RGD-BBN, J. Med. Chem., 52, 425–432 (2009).

 

  1. N. Amraee, et al., Human dose assessment of 68Ga-NODAGA-RGD-BBN heterodimer peptide based on animal data, J. Med. Phys, 47, 287-293 (2022)

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