developed. Using these methods, CNT will be labeled with 99mTc andconjugated with drugs that will be labeled with 111In; their behaviorwill be observed in vivo via biodistribution and SPECT imagingstudies. This strategy permits independent tracking of the compo-nents as they undergo distribution and clearance.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.113

4Higher carbonyl cores of Tc and Re bioconjugates: Prospectsand limitationsA.E. Miroslavov, G.V. Sidorenko, A.A. Lumpov,M.Yu. Tyupina, D.N. Suglobov

Khlopin Radium Institute, 2-i Murinskii pr. 28, St. Petersburg, 194021 Russia

Although [M(CO)3(H2O)3]+ cations (M= Tc or Re) are conve-nient precursors for tethering 99mTc or 186,188Re to biomolecules,introduction of M(CO)3 core into a biomolecule requires bulkytridentate chelators or a combination of mono- and bidentatecoordination units, which can negatively affect the native propertiesof the biomolecule. To minimize this influence, we suggestedtechnetium and rhenium penta- and tetracarbonyl cores in combi-nation with mono- (isocyanide) and bidentate (dithiocarbamate,xanthate) ligating units, respectively. The key point in this approachis stability of the resulting bioconjugates. We found that thecomplexes [M(CO)5(CN(CH2)nCOOEt)]+ (n = 1, 10) are sufficientlyresistant to thermal decarbonylation in solution. In the presence ofhistidine in aqueous solution, however, the rhenium complexdecomposes, whereas its Tc analog is much more stable. As for thetetracarbonyl core, [Tc(CO)4(Et2NCS2)] and [Tc(CO)4(MeCOS2)]readily undergo CO replacement in coordinating solvents to formtricarbonyl species, and [Tc(CO)4(Et2NCS2)] is also unstable withrespect to thermal decarbonylation. [Re(CO)4(MeCOS2)] appears tobe stable to both thermal decarbonylation and reaction with donorsolvents. Thus, technetium pentacarbonyl core in combination withisocyanide unit and rhenium tetracarbonyl core in combination withxanthate unit show promise for preparing bioconjugates.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.027

5Synthesis and biological evaluation of 99mTcO-MNXT as a noveltumor hypoxia imaging agentZhenxiang Li, Xuebin Wang, Junbo Zhang

Key Laboratory of Radiopharmaceuticals, Ministry of Education,College of Chemistry, Beijing Normal University, Beijing, 100875

In the development of hypoxia imaging agents, nitroimidazolederivatives are enzymatically reduced and accumulated in hypoxicregions, therefore most labeled probes for tumor hypoxia have beenbased on nitroimidazole analogues. In order to find a novel idealhypoxia imaging agent, MNXT (metronidazole xanthate) wassynthesized and radiolabeled with 99mTc-GH to form the 99mTcO–MNXT complex. The radiochemical purity of the 99mTcO–MNXTcomplex was over 90%, as measured by TLC. It was stable over 6 h atroom temperature. The partition coefficient results indicated that thiscomplex was hydrophilic. The tumor cell experiment and thebiodistribution in mice bearing S180 tumor showed that the 99mTcO–MNXT complex had a certain hypoxia selectivity and accumulated inthe tumor with high uptake and good retention. The tumor uptakes of99mTcO–MNXT were 5.48 ± 1.02 and 3.59 ± 0.81% ID/g at 2 h and 4 h

post-injection. The tumor uptake, tumor/blood and tumor/muscleratios at 4 h post-injection reached 3.59, 2.30 and 6.65, respectively.The significant tumor localization, good retention and high target/non-target ratios of the complex exhibited favorable properties, suggesting itcan be developed as a new tumor hypoxia imaging agent.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.063

6[CpM(CO)3] (M= Re, 99mTc) labeled phenylbenzothiazoles asimaging agents for Aβ plaquesJianhua Jia, Mengchao Cui, Boli Liu

Key Laboratory of Radiopharmaceuticals, Ministry of Education, Collegeof Chemistry, Beijing Normal University

The complexes of [CpM(CO)3] (M= Re, 99mTc) conjugating thephenylbenzothiazolewere synthesized and evaluated to detect amyloid-β (Aβ) deposition in the brain. The rhenium complexes 1–4were provedto have medium affinity for Aβ1–42 aggregates (Ki = 142, 76, 64 and24 nM, respectively) by in vitro binding assays. 99mTc complexes clearlymarked Aβ plaques on brain sections of Tg mice by in vitroautoradiography,which confirmed the sufficient affinities for Aβ plaques(Fig. 1). However, they did not show admirable property in respect ofinitial brain uptake (b0.5% ID/g), which hinders the further developmentof these tracers as SPECT probes for diagnosis of AD. Nonetheless, it isencouraging that these 99mTc-labeled complexes designed by conjugateapproach displayed sufficient affinity for Aβ plaques.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.057

7Synthesis and evaluation of single amino acid chelate (SAAC)tetrazine derivatives for bioorthogonal conjugation with Re/99mTcJohn F. Valliant, Ramesh Patel, Alyssa Vito

Department of Chemistry and Chemical Biology, McMaster University,Hamilton, Ontario, Canada

The inverse electron demand [4 + 2] Diels–Alder cycloadditionreaction between radiolabeled 1,2,4,5-tetrazines and biomolecule-derived strained alkenes has recently been used to create molecularimaging probes that generate exquisite target-to-non-target ratios[1]. The advantage of this pretargeting strategy is that short-lived

Fig. 1. Autoradiography of [99mTc]2 (n = 5, R = H) on brain sections of Tg andfluorescein staining with Th-S on partial enlarged detail.

Abstracts614