ACS Medicinal Chemistry Letters
Letter
(9) Li, Z.; Cui, M.; Dai, J.; Wang, X.; Yu, P.; Yang, Y.; Jia, J.; Fu, H.;
Ono, M.; Jia, H.; Saji, H.; Liu, B. Novel cyclopentadienyl tricarbonyl
complexes of (99m)Tc mimicking chalcone as potential single-photon
emission computed tomography imaging probes for beta-amyloid
plaques in brain. J. Med. Chem. 2013, 56, 471−482.
(10) Jia, J.; Cui, M.; Dai, J.; Liu, B. 2-Phenylbenzothiazole conjugated
with cyclopentadienyl tricarbonyl [CpM(CO)3] (M = Re, (99m)Tc)
complexes as potential imaging probes for beta-amyloid plaques.
Dalton Trans. 2015, 44, 6406−6415.
(11) Tzanopoulou, S.; Sagnou, M.; Paravatou-Petsotas, M.; Gourni,
E.; Loudos, G.; Xanthopoulos, S.; Lafkas, D.; Kiaris, H.; Varvarigou, A.;
Pirmettis, I. C.; Papadopoulos, M.; Pelecanou, M. Evaluation of Re and
(99m)Tc complexes of 2-(4′-aminophenyl)benzothiazole as potential
breast cancer radiopharmaceuticals. J. Med. Chem. 2010, 53, 4633−
4641.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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Experimental details for synthesis and characterization of
ferrocene precursor 3 and complexes Re-1 and 99mTc-1,
including 1H and 13C NMR spectroscopic data;
comparative HPLC for Re-1 and 99mTc-1; stability
studies of 99mTc-1; binding studies using Aβ42 fibrillar
aggregates and in vitro binding of Re-1 to amyloid
plaques; biodistribution and imaging studies (PDF)
(12) Tzanopoulou, S.; Pirmettis, I. C.; Patsis, G.; Paravatou-Petsotas,
M.; Livaniou, E.; Papadopoulos, M.; Pelecanou, M. Synthesis,
characterization, and biological evaluation of M(I)(CO)(3)(NNO)
complexes (M = Re, Tc-99m) conjugated to 2-(4-aminophenyl)-
benzothiazole as potential breast cancer radiopharmaceuticals. J. Med.
Chem. 2006, 49, 5408−5410.
(13) Sagnou, M.; Tzanopoulou, S.; Raptopoulou, C. P.; Psycharis, V.;
Braband, H.; Alberto, R.; Pirmettis, I. C.; Papadopoulos, M.;
Pelecanou, M. A Phenylbenzothiazole Conjugate with the Tricarbonyl
fac-[M(I)(CO)(3)](+) (M = Re, Tc-99, Tc-99m) Core for Imaging of
beta-Amyloid Plaques. Eur. J. Inorg. Chem. 2012, 2012, 4279−4286.
(14) Dey, J.; Dogra, S. K. Dual Fluorescence of 2-(4′-(N,N-
Dimethylamino)Phenyl)Benzothiazole and Its Benzimidazole Analog -
Effect of Solvent and pH on Electronic-Spectra. J. Phys. Chem. 1994,
98, 3638−3644.
(15) Dischino, D. D.; Welch, M. J.; Kilbourn, M. R.; Raichle, M. E.
Relationship between Lipophilicity and Brain Extraction of C-11-
Labeled Radiopharmaceuticals. J. Nucl. Med. 1983, 24, 1030−1038.
(16) Klunk, W. E.; Wang, Y.; Huang, G. F.; Debnath, M. L.; Holt, D.
P.; Mathis, C. A. Uncharged thioflavin-T derivatives bind to amyloid-
beta protein with high affinity and readily enter the brain. Life Sci.
2001, 69, 1471−1484.
(17) Yang, Y.; Cui, M.; Jin, B.; Wang, X.; Li, Z.; Yu, P.; Jia, J.; Fu, H.;
Jia, H.; Liu, B. (99m)Tc-labeled dibenzylideneacetone derivatives as
potential SPECT probes for in vivo imaging of beta-amyloid plaque.
Eur. J. Med. Chem. 2013, 64, 90−98.
(18) Yazdani, A.; Janzen, N.; Czorny, S.; Valliant, J. F. Technetium(I)
Complexes of Bathophenanthrolinedisulfonic Acid. Inorg. Chem. 2017,
56, 2958−2965.
(19) Oakley, H.; Cole, S. L.; Logan, S.; Maus, E.; Shao, P.; Craft, J.;
Guillozet-Bongaarts, A.; Ohno, M.; Disterhoft, J.; Van Eldik, L.; Berry,
R.; Vassar, R. Intraneuronal beta-amyloid aggregates, neurodegenera-
tion, and neuron loss in transgenic mice with five familial Alzheimer’s
disease mutations: potential factors in amyloid plaque formation. J.
Neurosci. 2006, 26, 10129−10140.
AUTHOR INFORMATION
Corresponding Author
ORCID
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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The authors thankfully acknowledge the generous contribution
of Professor David Mann of the Greater Manchester Neuro-
sciences Centre, University of Manchester in the AD brain
tissue staining experiments. They also thank Dr. Athina Tzinia
of the Laboratory of Cell & Matrix Biochemistry/Pathobiology,
Institute of Biosciences & Applications, NCSR “Demokritos”,
for kindly providing the 5xFAD transgenic mice.
REFERENCES
■
(1) Klunk, W. E.; Engler, H.; Nordberg, A.; Wang, Y.; Blomqvist, G.;
Holt, D. P.; Bergstrom, M.; Savitcheva, I.; Huang, G. F.; Estrada, S.;
Ausen, B.; Debnath, M. L.; Barletta, J.; Price, J. C.; Sandell, J.; Lopresti,
B. J.; Wall, A.; Koivisto, P.; Antoni, G.; Mathis, C. A.; Langstrom, B.
Imaging brain amyloid in Alzheimer’s disease with Pittsburgh
compound-B. Ann. Neurol. 2004, 55, 306−319.
(2) Bateman, T. M. Advantages and disadvantages of PET and
SPECT in a busy clinical practice. J. Nucl. Cardiol. 2012, 19, S3−S11.
(3) Bartholoma, M. D.; Louie, A. S.; Valliant, J. F.; Zubieta, J.
Technetium and gallium derived radiopharmaceuticals: comparing and
contrasting the chemistry of two important radiometals for the
molecular imaging era. Chem. Rev. 2010, 110, 2903−2920.
(4) Ono, M.; Saji, H. Recent advances in molecular imaging probes
for beta-amyloid plaques. MedChemComm 2015, 6, 391−402.
(5) Zhang, X.; Yu, P.; Yang, Y.; Hou, Y.; Peng, C.; Liang, Z.; Lu, J.;
Chen, B.; Dai, J.; Liu, B.; Cui, M. 99mTc-Labeled 2-Arylbenzothiazoles:
Abeta Imaging Probes with Favorable Brain Pharmacokinetics for
Single-Photon Emission Computed Tomography. Bioconjugate Chem.
2016, 27, 2493−2504.
(20) Jiang, L.; Zhang, M. K.; Tang, L.; Weng, Q. J.; Shen, Y. H.; Hu,
Y. Z.; Sheng, R. Identification of 2-subsituted benzothiazole derivatives
as triple-functional agents with potential for AD therapy. RSC Adv.
2016, 6, 17318−17327.
(21) Hroch, L.; Aitken, L.; Benek, O.; Dolezal, M.; Kuca, K.; Gunn-
Moore, F.; Musilek, K. Benzothiazoles - Scaffold of Interest for CNS
Targeted Drugs. Curr. Med. Chem. 2015, 22, 730−747.
(22) Gagoria, J.; Verma, P. K. Gaba-at Inhibitory Activity of
Benzothiazole - Gaba Analogs: In-Silico Approach for Antiepileptic
Profile. Int. J. Pharm. Sci. Res. 2016, 7, 4437−4442.
(6) Jia, J.; Zhou, K.; Dai, J.; Liu, B.; Cui, M. 2-Arylbenzothiazoles
labeled with [CpRe/99mTc(CO)3] and evaluated as beta-amyloid
imaging probes. Eur. J. Med. Chem. 2016, 124, 763−772.
(7) Bernard, J.; Ortner, K.; Spingler, B.; Pietzsch, H. J.; Alberto, R.
Aqueous synthesis of derivatized cyclopentadienyl complexes of
technetium and rhenium directed toward radiopharmaceutical
application. Inorg. Chem. 2003, 42, 1014−1022.
(8) Cui, M. Past and recent progress of molecular imaging probes for
beta-amyloid plaques in the brain. Curr. Med. Chem. 2014, 21, 82−112.
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