Preparation and preliminary biological evaluation of [153Sm] samarium AMD3100; towards a possible therapeutic chemokine receptor CXCR4 targeting complex

Document Type: Original Article

Authors

1 Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Nuclear Science Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

3 Clinic of Nuclear Medicine, University Medical Centre Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany

4 Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction: In continuation of recent development of possible C-X-C chemokine receptor type 4 (CXCR4) imaging agents, we report the development of a possible CXCR4 targeted therapy agent.
Methods: [153Sm]labeled 1,1′-[1,4-phenylenebis(methylene)] bis-1,4,8,11-tetraazacyclo -tetradecane ([153Sm]-AMD3100) was prepared using [153Sm]SmCl3 and AMD-3100 for 24h at 50°C in acetate buffer.Stability tests, partition coefficient determination, toxicity tests and biodistribution studies of the complex in wild-type rats were determined.
Results: The radiolabeled complex was prepared in high radiochemical purity (>95%; RTLC and >99% HPLC) and specific activity of 278 GBq/mmol and demonstrated significant stability up to 48h at 37 °C (in presence of human serum). Partition coefficient determination was calculated Log P= -1.09.Hepatotoxicity experiments demonstrated no distinguishable effect on hepatic enzymes in 10 days post injection.Initial complex biodistribution data showed significant liver and kidney accumulation in wild-type rats.

Conclusion: Since lung and spleen are considered as CXCR4 rich organs, the best lung/blood and spleen/blood ratios were achieved 12 and 7 at 24 h post injection. Further investigations are needed especially on therapeutic properties of this agent.

Keywords

Main Subjects


Balkwill F. Cancer and the chemokine network. Nat Rev Cancer. 2004 Jul;4(7):540-50.

Masuda M, Nakashima H, Ueda T, Naba H, Ikoma R, Otaka A, Terakawa Y, Tamamura H, Ibuka T, Murakami T. A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II). Biochem Biophys Res Commun. 1992 Dec 15;189(2):845-50.

Liang Z, Yoon Y, Votaw J, Goodman MM, Williams L, Shim H. Silencing of CXCR4 blocks breast cancer metastasis. Cancer Res. 2005 Feb 1;65(3):967-71.

Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res. 2004 Dec 1;64(23):8604-12.

Gerlach LO, Jakobsen JS, Jensen KP, Rosenkilde MR, Skerlj RT, Ryde U, Bridger GJ, Schwartz TW. Metal ion enhanced binding of AMD3100 to Asp262 in the CXCR4 receptor. Biochemistry. 2003 Jan 28;42(3):710-7.

Knight JC, Hallett AJ, Brancale A, Paisey SJ, Clarkson RW, Edwards PG. Evaluation of a fluorescent derivative of AMD3100 and its interaction with the CXCR4 chemokine receptor. Chembiochem. 2011 Nov 25;12(17):2692-8.

Zhang JM, Tian JH,  Li TR, Guo HY,  Shen L. 99mTc–AMD3100: A novel potential receptor-targeting radiopharmaceutical for tumor imaging. Chin Chem Lett 2010;21(4):461–463.

Jacobson O, Weiss ID, Szajek L, Farber JM, Kiesewetter DO. 64Cu-AMD3100--a novel imaging agent for targeting chemokine receptor CXCR4. Bioorg Med Chem. 2009 Feb 15;17(4):1486-93.

Nimmagadda S, Pullambhatla M, Stone K, Green G, Bhujwalla ZM, Pomper MG. Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography. Cancer Res. 2010 May 15;70(10):3935-44.

Aghanejad A, Jalilian AR, Fazaeli Y, Beiki D, Fateh B, khalaj A. Radiosynthesis and biodistribution studies of [62Zn/62Cu]–plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging. J Radioanal Nucl Chem. 2014;299(3):1635-1644.

Aghanejad A, Jalilian AR, Fazaeli Y, Alirezapoor B, Pouladi M, Beiki D, Maus S, Khalaj A. Synthesis and Evaluation of [(67)Ga]-AMD3100: A Novel Imaging Agent for Targeting the Chemokine Receptor CXCR4. Sci Pharm. 2013 Sep 12;82(1):29-42.

Marques F, Guerra KP, Gano L, Costa J, Campello MP, Lima LM, Delgado R, Santos I. 153Sm and 166Ho complexes with tetraaza macrocycles containing pyridine and methylcarboxylate or methylphosphonate pendant arms. J Biol Inorg Chem. 2004 Oct;9(7):859-72.

Ayati N, Aryana K, Jalilian AR, Hoseinnejad T, Bahrami Samani A, Ayati Z,  Shariati F, Zakavi SR. Treatment efficacy of 153Sm-EDTMP for painful bone metastasis. Asia Ocean J Nucl Med Biol. 2013;1(1):27-31.

Beiki D, Haddad P, Fallahi B, Keyvan A, Gholamrezanezhad A, Mirzaei H, Saghari M, Amouzegar-Hashemi F, Kazemian A, Fard-Esfahani A, Eftekhari M. Effectiveness and complications of 153Sm-EDTMP in palliative treatment of diffuse skeletal metastases. Iran J Nucl Med. 2013;21(1):26-32. 

IAEA-TECDOC-1340: Manual for reactor produced radioisotopes. Vienna: IAEA; 2003. p. 71.

Jalilian AR, Rowshanfarzad P, Sabet M, Novinrooz A, Raisali G. Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical.  J Radioanal Nucl Chem. 2005;264(3):617-621.

Woodard LE, Nimmagadda S. CXCR4-based imaging agents.  J Nucl Med. 2011 Nov;52(11):1665-9.

Nimmagadda S, Pullambhatla M, Pomper MG.  Immunoimaging of CXCR4 expression in brain tumor xenografts using SPECT/CT. J Nucl Med. 2009 Jul;50(7):1124-30.