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Low toxic ytterbium complexes of 2,4-dimethoxyhematoporphyrin IX for luminescence diagnostics of tumors

Schwach toxische Ytterbium-Komplexe von 2,4-Dimethoxyhematoporphyrin IX für die Lumineszenzdiagnostik von Tumoren
  • Andrey V. Ivanov , Valentina D. Rumyantseva , Igor P. Shilov EMAIL logo , Valerii M. Markushev , Andrey I. Panas , Alexandr S. Ryabov , Andrey F. Mironov , Georgii S. Terentyuk , Adrian Rühm , Anatolii Yu. Barishnikov and Kamil S. Shchamkhalov
Published/Copyright: July 23, 2013
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Abstract:

This article deals with the creation of new low-toxic photosensitizers on the basis of Ytterbium-2,4-dimethoxyhematoporphyrin IX (Yb-DMHP) and their application for the luminescence diagnostics of cancer. These substances were found to weakly generate singlet oxygen, exhibit pronounced luminescence, and retain the tumor-tropic properties of therapeutic photosensitizers. Basic photophysical properties of Yb-DMHP were studied, and the primary toxicological and pharmacokinetic investigations were performed in the organisms of experimental animals. The 4f-luminescence of Yb-DMHP in the near infrared (NIR) spectral region was observed. Comparative investigations were performed for one of the photodynamic medications which have been approved for clinical application: “Photoditazin”, a diglucosamine salt of chlorin e6. It was shown that the efficiency of singlet oxygen generation is lower by approximately one order of magnitude in the case of Yb-DMHP. The experimental data prove that Yb-DMHP-based substances are promising as non-toxic markers for the luminescence diagnostics of malignant tumors in the NIR spectral range (900–1100 nm), because they are free of the phototoxicity that is typical of conventional porphyrins, while at the same time providing a relatively high luminescence contrast and a selective accumulation in tumor tissue.

Zusammenfassung

Dieser Artikel befasst sich mit der Entwicklung neuer schwach toxischer Photosensibilisatoren auf der Basis von Ytterbium-2,4-Dimethoxyhematoporphyrin IX (Yb-DMHP) und ihrer Anwendung für die Lumineszenzdiagnose von Krebs. Es hat sich gezeigt, dass diese Substanzen nur geringe Mengen an Singulett-Sauerstoff erzeugen, eine ausgeprägte Lumineszenz aufweisen und die tumortropen Eigenschaften von therapeutischen Photosensibilisatoren behalten. Grundlegende photophysikalische Eigenschaften von Yb-DMHP wurden untersucht, primäre toxikologische und pharmakokinetische Untersuchungen in den Organismen von Versuchstieren durchgeführt sowie die 4f-Lumineszenz im nahen Infrarot (NIR)-Spektralbereich beobachtet. Vergleichende Untersuchungen wurden für eines der photodynamischen Medikamente, die für die klinische Anwendung zugelassen sind, durchgeführt: „Photoditazin“, ein Glucosaminsalz des Chlorin e6. Es wurde gezeigt, dass die Effizienz der Erzeugung von Singulett-Sauerstoff bei Yb-DMHP um ungefähr eine Größenordnung geringer ist. Die experimentellen Daten erwiesen sich als vielversprechend und deuten darauf hin, dass Yb-DMHP-basierte Stoffe als ungiftige Marker für die Lumineszenzdiagnostik von malignen Tumoren im NIR-Spektralbereich (900–1100 nm) einsetzbar sind, da sie frei von Phototoxizität sind (die typisch für herkömmliche Porphyrine ist) und gleichzeitig einen relativ hohen Lumineszenzkontrast und eine selektive Anreicherung im Tumorgewebe aufweisen.


Corresponding author: Igor P. Shilov, Kotel’nikov Institute of Radio Engineering and Electronics (Fryazino Branch), Russian Academy of Sciences, pl. Vvedenskogo 1, Fryazino, Moscow oblast, 141190, Russia

This work was supported by the International Science and Technology Center (project no. 3065). The work was partially supported by the Programs of Presidium of Russian Academy of Sciences “Basic Research for Medicine”.

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Erhalten: 2013-1-10
Revidiert: 2013-5-2
Angenommen: 2013-5-28
Online erschienen: 2013-7-23
Erschienen im Druck: 2013-8-1

©2013 by Walter de Gruyter Berlin Boston

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