Synthesis of [(125)I]iodoDPA-713: a new probe for imaging inflammation.
[(125)I]IodoDPA-713 [(125)I]1, which targets the translocator protein (TSPO, 18 kDa), was synthesized in seven steps from methyl-4-methoxybenzoate as a tool for quantification of inflammation in preclinical models. Preliminary in vitro autoradiography and in vivo small animal imaging were performed using [(125)I]1 in a neurotoxicant-treated rat and in a murine model of lung inflammation, respectively. The radiochemical yield of [(125)I]1 was 44+/-6% with a specific radioactivity of 51.8 GBq/micromol (1400 mCi/micromol) and >99% radiochemical purity. Preliminary studies showed that [(125)I]1 demonstrated increased specific binding to TSPO in a neurotoxicant-treated rat and increased radiopharmaceutical uptake in the lungs of an experimental inflammation model of lung inflammation. Compound [(125)I]1 is a new, convenient probe for preclinical studies of TSPO activity.
Wang
Haofan
H
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Pullambhatla
Mrudula
M
Guilarte
Tomas R
TR
Mease
Ronnie C
RC
Pomper
Martin G
MG
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging*; D051379:Mice; D008815:Mice, Inbred Strains; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011014:Pneumonia / Q000000981:diagnostic imaging; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D018079:Receptors, GABA / Q000032:analysis* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D000081:Acetamides; D015335:Molecular Probes; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C544082:N,N-diethyl-2-(2-(3-iodo-4-methoxyphenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
J Nucl Med. 2007 Apr;48(4):573-81
17401094
J Nucl Med. 2009 Aug;50(8):1276-82
19617321
J Med Chem. 2009 Feb 12;52(3):581-92
19133775
Exp Neurol. 2009 Apr;216(2):459-70
19320004
Bioorg Med Chem. 2005 Nov 15;13(22):6188-94
16039131
J Nucl Med. 2009 Mar;50(3):468-76
19223401
Pharmacol Ther. 2008 Apr;118(1):1-17
18374421
Neuroscience. 2009 Feb 6;158(3):1161-73
18983900
Neurotherapeutics. 2007 Jul;4(3):443-52
17599710
J Immunol Methods. 1997 Mar 10;202(1):49-57
9075771