Zn Complex of Diaminedithiol Tetradentate Ligand as a Stable Precursor for 99mTc-Labeled Compounds

The diaminedithiol (N2S2) tetradentate ligand constitutes a useful chelating molecule for preparing 99mTc-labeled compounds of high in vivo stability in high radiochemical yields. However, since the thiol groups in the N2S2 ligand are easy to be oxidized to disulfide bonds, they need to be protected with an appropriate protecting group, which hinders the broad applications of the N2S2 ligand for radiopharmaceuticals. In this study, a Zn chelate of N2S2 was evaluated as a precursor for purification-free 99mTc-labeled N2S2 under the mild and simple procedure. Zn-N2S2 was prepared by reacting Zn acetate with N2S2, and the Zn-N2S2 remained stable under aerobic conditions at room temperature. 99mTc-N2S2 was obtained over 90% radiochemical yields at room temperature by a one-pot reaction, consisting of Zn-N2S2 (10−5 M), 99mTcO4−, ethylenediaminetetraacetic acid (EDTA), and a reducing agent (Sn2+) at pH = 5.5 to 7.5. 99mTc-N2S2 was also obtained over 90% radiochemical yields when the reaction was conducted in the presence of an equimolar amount of IgG antibody. These findings indicate the Zn complex of N2S2 ligand constitutes a stable and useful precursor to prepare 99mTc-labeled N2S2 compounds in high yields under the mild and simple procedure

A Novel SPECT Tracer for Cerebral Amyloid and Tau Aggregates Accumulated in Alzheimer\u27s Disease and related tauopathy

BACKGROUND: Non-invasive determination for amyloid- (A) plaques and neurofibrillary tangles (NFTs) has important significance for early diagnosis and medical intervention to Alzheimer’s disease (AD) and related tauopathies. Although several single photon emission computed tomography (SPECT) tracers for Aplaques imaging were reported, to the best of our knowledge, no tracer is successful for tau imaging in the living brains. PURPOSE: In the present study, we have developed a novel SPECT tracer AD-DRK for A and tau deposition for in-vivo detection.METHODS: 125I-labeled AD-DRK ([125I] AD-DRK) was designed and synthesized based on our previous publication. The biodistribution was determined in normal mice. The detectability of Ab and tau deposition was investigated by in-vitro and ex-vivo autoradiography in APP and tauopathy mouse models, and post-mortem human brains.RESULTS: [125I] AD-DRK showed high initial brain uptake with a peak value of approximately 7% of injection dose per ml at 2 minute post-injection and rapid washout thereafter. In vitro autoradiography has clearly demonstrated that there was overt specific binding of [125I] AD-DRK in temporal cortex region of AD or progressive supranuclear palsy (PSP) enriched with A plaques and/or neurofibrillary tangle. Moreover, ex vivo autoradiographic analysis showed that [125I] AD-DRK has higher accumulation in forebrain enriched with A or tau accumulation in AD and tauopathy mouse models compared with normal mouse, implying the utility of AD-DRK for in-vivo imaging for A and/or tau deposition.CONCLUSION: [125I] AD-DRK has demonstrated high potential as SPECT ligand for diagnosis for AD and/or related tauopathies.THE 13TH ASIA OCEANIA CONGRESS OF NUCLEAR MEDICINE AND BIOLOG