title: Synthesis and evaluation of a new class of technetium-99m monocationic radiotracers from dithienyldiazalkanes.
abstract: Monocationic 99mTc complexes, [99mTcO2 (THEN)]+ and [99mTcO2(THPN)]+ derived from a new class of N2S2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5-diazahexane (THEN) and 1,7-di- (2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN), have been synthesized using Sn(II) tartrate reduction of [99mTc]pertechnetate at pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate anion (CF3SO3-) in high radiochemical yield (approximately 90%). Radiochemical analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300 DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone) revealed high radiochemical purity (> 90%). High octanol-saline partition coefficients (> 37) of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ indicated a lipophilic nature of the complexes. Relative stability of the 99mTc complex was high as measured by DTPA challenge studies. Biodistribution of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ in rats at 15 min post-injection showed heart-to-blood activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance. Further studies involving the variation of substituents on the basic core structure of this new class of 99mTc complexes may provide radiotracers suitable for myocardial imaging.
authors.affiliation: University of Texas Southwestern Medical Center at Dallas 75235-9058, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Goomer
authors.forename: P V
authors.initials: PV
authors.lastname: Kulkarni
authors.forename: A
authors.initials: A
authors.lastname: Constantinescu
authors.forename: P
authors.initials: P
authors.lastname: Antich
authors.forename: R W
authors.initials: RW
authors.lastname: Parkey
authors.forename: J R
authors.initials: JR
authors.lastname: Corbett
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005069:Evaluation Studies as Topic; D007553:Isotope Labeling; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013876:Thiophenes; C107828:technetium Tc 99m 1,6-di-(2-thienyl)-2,5-diazahexane; C107829:technetium Tc 99m 1,7-di-(2-thienyl)-4,4-dimethyl-2,6-diazaheptane