The macrocyclic bone-seeking agent DO2A2P bears a cyclen core and two

The macrocyclic bone-seeking agent DO2A2P bears a cyclen core and two pairs of peripheral phosphonate and carboxylate groups. partition coefficients (logP) in a biphasic solvent system of stability of both complexes was evaluated in rat serum by radio-TLC. Both complexes remained virtually intact (> 98%) out to 7 days.16 The comparative binding of 177Lu-labeled bone-seeking profiles a SPECT/CT imaging study was performed in normal BALB/c mice using both 177Lu-distribution patterns in that they preferentially accumulated in the spine and the bone joints at 1 h post-injection. The quantitative analysis of the SPECT/CT images revealed the bone uptake levels of 177Lu-sagittal and coronal: … Taken together no significant difference was observed for the 177Lu-labeled geometric isomer pair of DO2A2P in their biological properties assayed in this work. Acknowledgments This work was partially supported by an NIH R21 grant (CA119219) an NIH NCRR grant (1S10RR029674-01) and the Dr. Jack Krohmer Professorship Funds. Footnotes Publisher’s Disclaimer: This is a PDF file MTEP hydrochloride of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting typesetting and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content and all legal disclaimers that apply to the journal pertain. References and notes 1 Mundy GR. Nat. Rev. Cancer. 2002;2:584. [PubMed] 2 Palma E Correia JD Campello MP Santos I. Mol Biosyst. 2011;7:2950. [PubMed] 3 Hao G Singh AN Liu W Sun X. Curr. Top. Med. Chem. 2010;10:1096. [PubMed] 4 Brechbiel MW. Q J Nucl Med. 2008;52:166. [PMC free article] [PubMed] 5 Liu W Hajibeigi A Lin M Rostollan CL Kovacs Z Oz OK Sun X. Bioorg. Med. Chem. Lett. 2008;18:4789. [PMC free article] [PubMed] 6 Suzuki K Satake M Suwada J Oshikiri S Ashino H Dozono H Hino A Kasahara H Minamizawa T. Nucl Med Biol. 2011;38:1011. [PubMed] 7 Gano L Marques F MTEP hydrochloride Campello MP Balbina M Lacerda S Santos I. Q J Nucl Med. 2007;51:6. [PubMed] 8 Campello MP Lacerda S Santos IC Pereira GA Geraldes CF Kotek J Hermann P Vanek J Lubal P Kubicek V Toth E Santos I. Chem. Eur. J. MTEP hydrochloride 2010;16:8446. [PubMed] 9 Kalman FK Baranyai Z Toth I Banyai I Kiraly R Brucher E Aime S Sun X Sherry AD Kovacs Z. Inorg. Chem. 2008;47:3851. [PubMed] 10 Campello MP Marques F Gano L Lacerda S Santos I. Radiochim. Acta. 2007;95:329. 11 Li C Wong WT. BMP2B J Org Chem. 2003;68:2956. [PubMed] 12 Chemical synthesis and characterization data: Paraformaldehyde (0.16 g) was added to a mixture of 1 4 ester (1) (1.00 g 2.5 mmol) and triethyl phosphate (0.95 g 5 mmol). The mixture was stirred for 4 days at room temperature. The volatile impurities were removed in vacuum at 60 °C for 1 day to yield clear oil that consisted of the ester intermediate (2: di-tert-butyl 2 2 10 4 7 10 4 and a small amount of diethyl hydroxymethyl phosphonate. It was dissolved in hydrochloric acid (20% 30 mL) and the solution was refluxed for 2 days. The hydrochloric acid was removed by rotary evaporation and the residue was redissolved in water treated with activated carbon (0.5 g) filtered and evaporated again. The residue was redissolved in a small amount of water (3 mL) and ethanol (30 mL) was added in small portions. A white amorphous solid precipitated. The solution was decanted and the residue was redissolved in water (5 mL) and the crystallization of MTEP hydrochloride the product was induced by the addition of ethanol (5 mL). The mixture was stirred for 24 h. The white crystalline solid was filtered washed with water (2 × 3 mL) and dried to give 0.7 g or experiments were prepared by dissolving salts in Milli-Q water ( 8 MΩ cm) and then treated with Bio-Rad Chelex 100 resin for removal of trace metal ions. Lu-177 in 0.05 N HCl was purchased from University of Missouri Research Reactor. To 100 μL of the DO2A2P ligand solution (5 mM in 0.4 M NH4OAc buffer pH 6.5) 177 (ca. 37 MBq/1 mCi) in 0.05 N HCl was added. The reaction mixture was incubated at three temperature conditions (r.t. 50 °C and 90 °C). The formation of 177Lu-labeled DO2A2P was monitored by radio thin layer chromatography (radio-TLC). Radio-TLC was performed using a Rita Star Radioisotope TLC Analyzer (Straubenhardt Germany) on Whatman TLC plate KC18F reverse phase plate developed by 10% NH4OAc: MeOH (v/v 1:1) as the mobile phase. Under the TLC condition employed 177 labeled serum stability.