PREPARATION AND IN VITRO STABILITY STUDY OF 188Re-HEDP AS A BONE SEEKING RADIOPHARMACEUTICAL

  • Toni Tripunoski Institute of Pathophysiology and Nuclear Medicine, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Domokos Mathe Frederic Joliot-Curie National Institute of Radiobiology and Radiohygiene, Dept. of Applied Radioisotopes, Budapest, Hungary
  • Lajos Balog Frederic Joliot-Curie National Institute of Radiobiology and Radiohygiene, Dept. of Applied Radioisotopes, Budapest, Hungary
  • Ana Ugrinska Department of Radioisotopes and Radiopharmaceuticals Production, University Institute of Positron Emission Tomography, Skopje, North Macedonia
  • Maja Chochevska Department of Radioisotopes and Radiopharmaceuticals Production, University Institute of Positron Emission Tomography, Skopje, North Macedonia
  • Sinisha Stojanoski Institute of Pathophysiology and Nuclear Medicine, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Elena Stanojevska Institute of Pathophysiology and Nuclear Medicine, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Nevena Manevska Institute of Pathophysiology and Nuclear Medicine, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Toni Grozdanovski Institute of Epidemiology and Biostatistics with Medical Informatics, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Daniela PopGjorceva Institute of Pathophysiology and Nuclear Medicine, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia

Abstract

The majority of patients with bone metastases will require some kind of therapy for bone pain palliation with the objective of improving the quality of live(1). Bone seeking radiopharmaceuticals emitting beta particles have been used for palliation of bone metastases. Recently, scientists propose a slightly different radionuclide, 188Re that shows such promise for treating primary and metastatic tumors as a radiopharmaceutical 188Re-HEDP. 188Re-HEDP is a chemical complex of a bisphosphonate ligand with an incorporated atom of radioactive 188Re. Bisphosphonates are ligands that contain the P-C-P bond which makes the molecules resistant to breakdown by enzymatic hydrolysis and are chemically very stable. In this study, we showed the conditions for the labeling of HEDP with 188Re, and the in vitro stability of the radiopharmaceutical complex. 188Re-HEDP is intended for the treatment of patients whose condition often requires for the therapeutic dose to be transported to the institution where the patient is hospitalized. Our stability study is performed in order to determine the optimal storage conditions of the radiopharmaceutical if it is not applied to a patient immediately after preparation. The results of radiochemical purity of 188Re HEDP using ITLC quality control technique was above 98%. The stability study for 188Re HEDP stored at different ambiental conditions showed that the complex is most stable in the first 3 hours after preparation, if it is stored at +4oC in the dark. It can be concluded that the prescribed preparation conditions (composition and concentration of chemical components, temperature and incubation time) are optimal for the formation of high percentage and stable initial chelating complex of 188Re-HEDP.


Keywords: bone pain palliation, radionuclide therapy, radiopharmaceuticals, Rhenium-188.

References

1.Liepe K. 188Re-HEDP therapy in the therapy of painful bone metastases. World J Nucl Med. 2018;17(3):133-138. doi: 10.4103/wjnm.WJNM_85_17.
2.Body JJ, Rationale for the use of bisphosphonates in osteoblastic and osteolytic bone lesion, The Breast, 2003; 2:37-44.
3.Lin WY et all., Effect of reaction conditions on preparations of rhenium-188 hydroxyethylidene diphosphonate complexes, Nuclear medicine and Biology, 1999; 26(4):455-459.
4.Hsieh BT et all., Comparison of various rhenium-188-labeled diphosphonates for the treatment of bone metastases, Nuclear medicine and Biology, 1999; 26(8):973-976.
5.Kleynhans J, Duatti A, Bolzati C. Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry. Molecules. 2023; 28(3):1487. https://doi.org/10.3390/molecules28031487.
6.Faintuch BL, Faintuch S et Muramoto E, Complexation of 188Re-phosphonates: in vitro and in vivo studies, Radiochim. Acta, 2003; 91: 607-612.
7.Sijin L, Jianzhong L, Hong Z, Mei T, Jin W, Xiaoge Z, Rhenium-188 HEDP To Treat Painful Bone Metastases, Clin. Nuc. Med., 2001; 26(11): 919-922.
8.Lee JS, Lee JS, Park UJ, Son KJ, Han HS., Development of a high performance 188W/188Re generator using synthetic alumina. Appl Radiat Isot. 2009; 67:1162–6. doi: 10.1016/j.apradiso.2009.02.062.
9.Vucina J, Lukic D., Radionuclidic generators for the production of technetium-99m end rhenium-188, Phys. Chem. And Techn. 2002; 2(4):235-243.
10.Vallabhajosula S, Killeen RP, Osborne JR. Altered biodistribution of radiopharmaceuticals: role of radiochemical/pharmaceutical purity, physiological, and pharmacologic factors. Semin Nucl Med. 2010; 40(4):220-41. doi: 10.1053/j.semnuclmed.2010.02.004. PMID: 20513446.
11.Zuckier LS, Martineau P. Altered biodistribution of radiopharmaceuticals used in bone scintigraphy. Semin Nucl Med. 2015; 45(1):81-96. doi: 10.1053/j.semnuclmed.2014.07.007. PMID: 25475381.
12.Molavipordanjani S and Hosseinimehr SJ. Fundamental concepts of radiopharmaceuticals quality Controls. Pharm Biomed Res 2018; 4(3):1-8.
13.Kothari K, Pillai MR, Unni PR, Shimpi HH, Noronha OP, Samuel AM., Preparation, stability studies and pharmacological behavior of [186Re]Re-HEDP, Applied Radiation and IsotopeS. 1999; 51:51-58.
14.Lepareur N, Lacoeuille F, Bouvry C, Hindré F, Garcion E, Chérel M, Noiret N, Garin E and Knapp FFR JR., Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives. Front. Med. 2019; 6:132. doi: 10.3389/fmed.2019.00132.
15.Sampson CB and Keegan J., Stability of 99mTc-DTPA injection: effect of delay after preparation, dilution, generator oxidant, air and oxygen, NM Comm. 1985; 6:313-318.
Published
2023-12-27
How to Cite
TRIPUNOSKI, Toni et al. PREPARATION AND IN VITRO STABILITY STUDY OF 188Re-HEDP AS A BONE SEEKING RADIOPHARMACEUTICAL. Journal of Morphological Sciences, [S.l.], v. 6, n. 3, p. 148-156, dec. 2023. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol6no3-19>. Date accessed: 21 dec. 2024.
Section
Articles