Preparation, quality control and biodistribution study of 68Ga-BPAMD: Optimized production with an in-house 68Ge-68Ga generator

Document Type: Original Article

Authors

1 Energy Engineering and Physics Department, Amirkabir University of Technology, Tehran, Iran

2 Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

Abstract

Introduction: Bone metastases are common in the progression of various tumors leading to severe pain and decrease in quality of life. The aim of this study was to optimize the production of 68Ga-BPAMD as an ideal bone imaging agent using an in-house 68Ge/68Ga generator for future clinical use.
Methods: The optimized conditions for the preparation of 68Ga-BPAMD were determined by varying ligand concentration, pH, time and temperature. The radiochemical purity of the complex was checked using ITLC method. The stability at room temperature and in human serum and the hydroxyapatite (HA) binding of the complex were studied. Biodistribution of 68Ga-BPAMD and 68GaCl3 were investigated in male Syrian rats.
Results:The radiolabelled compound was prepared with a radiochemical purity of >99% after 15 min at the optimized conditions (30 µg of ligand, 90 °C, pH=3-5). The complex was stable in the final preparation and in the presence of human serum (>98%). HA binding assay demonstrated that at the amount of 10 and 25 mg of HA, 62.3 and 88.5 % of the complex are bound to HA, respectively. The agent demonstrated significant accumulation in the bone tissue, while cleared very fast from blood circulation. Major difference in uptake between 68Ga-BPAMD and 68GaCl3 was observed especially in blood, bone, liver, and spleen which can be considered as favorable characteristics of this agent.
Conclusion: According to these results, this agent can be produced with the recently developed in-house generator and considered as a worthy bone PET imaging agent available for further clinical use.

Keywords

Main Subjects


  1. Singh VA, Haseeb A, Alkubaisi AA. Incidence and outcome of bone metastatic disease at University Malaya Medical Centre. Singapore Med J. 2014 Oct;55(10):539-46.
  2. Kuchuk I, Hutton B, Moretto P, Ng T, Addison CL, Clemons M. Incidence, consequences and treatment of bone metastases in breast cancer patients-Experience from a single cancer centre. J Bone Oncol. 2013 Oct 3;2(4):137-44.
  3. Cook GJ, Azad GK, Goh V. Imaging bone metastases in breast cancer: Staging and response assessment. J Nucl Med. 2016 Feb;57 Suppl 1:27S-33S.
  4. Heindel W, Gübitz R, Vieth V, Weckesser M, Schober O, Schäfers M. The diagnostic imaging of bone metastases. Dtsch Arztebl Int. 2014 Oct 31;111(44):741-7. 
  5. Cuccurullo V1, Cascini GL, Tamburrini O, Rotondo A, Mansi L. Bone metastases radiopharmaceuticals: an overview. Curr Radiopharm. 2013 Mar;6(1):41-7.
  6. Nilegaonkar S, Sonar S, Ranade A, Khadilkar M.  TC99m MDP bone scan in evaluation of painful scoliosis. Indian J Nucl Med. 2010;25(2):67-69.
  7. Araz M, Aras G, Küçük ÖN.  The role of 18F-NaF PET/CT in metastatic bone disease. J Bone Oncol. 2015 Sep 16;4(3):92-7.
  8. Banerjee SR, Pomper MG. Clinical applications of Gallium-68. Appl Radiat Isot. 2013 Jun;76:2-13.
  9. Jalilian AR. An overview on Ga-68 radiopharmaceuticals for positron emission tomography applications. Iran J Nucl Med. 2016;24(1):1-10.
  10. Naderi M, Zolghadri S, Yousefnia H, Ramazani A, Jalilian AR. Preclinical study of 68Ga-DOTATOC: Biodistribution assessment in syrian rats and evaluation of absorbed dose in human organs. Asia Ocean J Nucl Med Biol. 2016 Winter;4(1):19-29.
  11. Fellner M, Baum RP, Kubícek V, Hermann P, Lukes I, Prasad V, Rösch F. PET/CT imaging of osteoblastic bone metastases with (68)Ga-bisphosphonates: first human study. Eur J Nucl Med Mol Imaging. 2010 Apr;37(4):834.
  12. Mirzaei A, Jalilian AR, Aghanejad A, Mazidi M, Yousefnia H, Shabani G, Ardaneh K, Geramifar P, Beiki D. Preparation and Evaluation of (68)Ga-ECC as a PET Renal Imaging Agent. Nucl Med Mol Imaging. 2015 Sep;49(3):208-16.
  13. Aghanejad A, Jalilian AR, Maus S, Yousefnia H, Geramifar P, Beiki D. Optimized production and quality control of 68Ga-Dotatate. Iran J Nucl Med. 2016;24(1):29-36.   
  14. Yousefnia H, Zolghadri S, Jalilian AR. Preparation and biodistribution assessment of 111In-BPAMD as a novel agent for bone SPECT imaging. Radiochim Acta. 2015;103(9):653-661.
  15. Doroudi A, Saadati SM, Ahmadi F, khodayar J, Rezaee S, Heidari Kaydan H. The effect of prednisolone on the sensitivity of Technetium 99m-methylene diphosphonate ( 99m Tc-MDP) scintigraphy to detect simulated closed fracture in the rat tibia. Iran J Nucl Med 2012;20(1):32-38.
  16. Fellner M, Baum RP, Kubícek V, Hermann P, Lukes I, Prasad V, Rösch F. PET/CT imaging of osteoblastic bone metastases with (68)Ga-bisphosphonates: first human study. Eur J Nucl Med Mol Imaging. 2010 Apr;37(4):834.