Indium-111 maltolate complex as a cell labeling agent for SPECT imaging

Document Type : Original Article

Authors

Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran, Tehran, Iran

Abstract

Introduction: Due to the cell labeling potentials of various metal-maltol complexes, the idea of developing a possible cell labeling imaging agent using single photon emission computed chromatography (SPECT) with[111In]-maltolate complex has been investigated.
Methods: [111In] labeled 3-hydroxy-2-methyl-4H-pyran-4-onate ([111In]-maltolate) was prepared using freshly prepared [111In]InCl3 and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 45°C. Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound followed by biodistribution and imaging studies. [111In]-maltolate was successively used in the radiolabeling of red blood cells for diagnostic studies.
Results: The complex was prepared successfully (radiochemical purity: >98% ITLC, >98% HPLC, specific activity: 15-17 GBq/mmol, log P=0.278). The complex is mostly washed out from the circulation through kidneys in 24h. the cell labeling efficacy was significant at the time of experiment.

Conclusion: [111In]-maltolate can be an interesting cell imaging agent due to stability and cell avidity of metal maltol complexes, however, further biodistribution studies in various cells as well as diagnostic protocols is necessary.

Keywords

Main Subjects


Jalilian AR, Bineshmarvasti M, Sardari S. Application of radioisotopes in inflammation. Curr Med Chem. 2006;13(8):959-65.
Aktolun C, Ussov WY, Arka A, Glass D, Gunasekera RD, Peters AM. Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies. Eur J Nucl Med. 1995 Apr;22(4):330-4.
Peters AM, Roddie ME, Danpure HJ, Osman S, Zacharopoulos GP, George P, Stuttle AW, Lavender JP. 99Tcm-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes. Nucl Med Commun. 1988 Jun;9(6):449-63.
Datz FL. Indium-111-labeled leukocytes for the detection of infection: current status. Semin Nucl Med. 1994 Apr;24(2):92-109.
Jalilian AR, Hakimi A, Garousi J, Bolourinovin F, Kamali-Dehghan M, Aslani G. Development of [201Tl](III)oxinate complex for in vitro cell labeling. Iran J Radiat Res. 2008;6(3):145-150.
Jalilian AR, Vakili A, Nazari S, Bolourinovin F, Rajabifar S, Optimization of [67Ga]-oxinate complex formation conditions for white blood cell labeling. J Nucl Sci Technol. 2010;52:67-71.
Jalilian AR, Rowshanfarzad P, Yari-Kamrani Y, Sabet M, Majdabadi A. Preparation and evaluation of [55Co](II)DTPA for blood cell labeling, The Open Inorg Chem J. 2009;3:21-25.
Jalilian AR, Rowshanfarzad P, Sabet M, Rahiminejad-Kisomi A, Rajamand AA. Development of [66Ga]Oxine Complex: a possible PET tracer. Nukleonika. 2006;51(3):155-159.
Ellis BL, Duhme AK, Hider RC, Hossain MB, Rizvi S, van der Helm D. Synthesis, physicochemical properties, and biological evaluation of hydroxypyranones and hydroxypyridinones: novel bidentate ligands for cell-labeling. J Med Chem. 1996 Sep 13;39(19):3659-70.
Bernstein LR, Tanner T, Godfrey C, Noll B. Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Met Based Drugs. 2000;7(1):33-47.
Thompson KH, Barta CA, Orvig C. Metal complexes of maltol and close analogues in medicinal inorganic chemistry. Chem Soc Rev. 2006 Jun;35(6):545-56.
Chitambar CR, Purpi DP, Woodliff J, Yang M, Wereley JP. Development of gallium compounds for treatment of lymphoma: gallium maltolate, a novel hydroxypyrone gallium compound, induces apoptosis and circumvents lymphoma cell resistance to gallium nitrate. J Pharmacol Exp Ther. 2007 Sep;322(3):1228-36.
Satoh E, Yasuda I, Yamada T, Suzuki Y, Ohyashiki T. Involvement of NO generation in aluminum-induced cell death. Biol Pharm Bull. 2007 Aug;30(8):1390-4.
Liu ZD, Piyamongkol S, Liu DY, Khodr HH, Lu SL, Hider RC. Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: novel iron chelators with enhanced pFe3+ values. Bioorg Med Chem. 2001 Mar;9(3):563-73.
Finnegan MM, Lutz TG, Nelson WO, Smith A, Orvig C. Neutral water-soluble post-transition-metal chelate complexes of medical interest: aluminum and gallium tris(3-hydroxy-4-pyronates). Inorg Chem. 1987;26:2171-76.
Naseri Z, Hakimi A, Jalilian AR, Nemati Kharat A, Bahrami-Samani A, Ghannadi-Maragheh M. Preparation and quality control of the [sm]-samarium maltolate complex as a lanthanide mobilization product in rats. Sci Pharm. 2011 Jun;79(2):265-75.
Fazaeli Y, Jalilian AR, Mohammadpour Amini M, Majdabadi A, Rahiminejad A, Bolourinovin F, Pouladi M. Development of Ga-67 maltolate complex as an imaging agent. Iran J Pharmaceut Res. 2012;11 (3):755-62.
Monga V, Patrick BO, Orvig C. Group 13 and lanthanide complexes with mixed O,S anionic ligands derived from maltol. Inorg Chem. 2005 Apr 18;44(8):2666-77.
Abeysinghe RD, Ellis BL, Porter JB. Platelet labelling with indium-hydroxypyridinone and indium-hydroxypyranone complexes. Eur J Nucl Med. 1994 Oct;21(10):1141-7.
Sadeghpour H, Jalilian AR, Akhlaghi M, Kamali-Dehghan M, Mirzaii M Shafiee A. Preparation and Biodistribution of [111In]-rHuEpo for Erythropoietin Receptor Imaging. J Radioanal Nucl Chem. 2008;278:117-22.
Marczenko Z. Spectrophotometric determination of elements. New York: John Wiley & Sons; 1976. p. 238-240.
Marczenko Z. Spectrophotometric determination of elements. New York: John Wiley & Sons; 1976. p. 176-179.
Rao SA, Dewanjee MK. Comparative evaluation of red cell-labeling parameters of three lipid-soluble- 111In-chelates: effect of lipid solubility on membrane incorporation and stability constant on transchelation. Eur J Nucl Med. 1982;7(6):282-5.
Moretti JL, Caglar M, Weinmann P. Cerebral perfusion imaging tracers for SPECT: which one to choose? J Nucl Med. 1995 Mar;36(3):359-63.