Optical imaging probes and their potential contribution to radiotracer development

 

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Summary

Optical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.

Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

Zusammenfassung

Die optische Bildgebung galt lange als Domäne der Histologie und Mikroskopie. In den vergangenen 15 Jahren hielt sie jedoch Einzug in die präklinische Bildgebung und zeigt in jüngster Zeit auch ihr Potenzial in klinischen Anwendungen (z. B. intraoperativ oder in der Bildgebung von entzündlichen Veränderungen). Die Entwicklung und präklinische Anwendung von neuen Farbstoffen und Zielstruktur-spezifischen Farbstoffkonjugaten liefern Informationen in Bezug auf charakteristische Ausscheidungswege und Bioverteilung, die wiederum in der Entwicklung und Optimierung radiopharmazeutischer Tracer genutzt werden können. Vor allem ionische Ladungen haben hier einen großen Einfluss und selbst die Summe und Verteilung von positiven und negativen Ladungen auf einem Farbstoff-Konjugaten kann darüber entscheiden, ob durch unspezifische Aufnahme ein starkes oder sehr geringes Hintergrundsignal in Leber, Niere oder Dünndarm resultiert.

Die Übertragung der Erkenntnisse der Biodistribution von Farbstoffen und Farbstoffkonjugaten auf die Neu- und Weiterentwicklung von Radiopharmaka erscheint viel versprechend und lässt eine weiter verbesserte Biodistribution und Verfügbarkeit eines Radio-pharmakons am jeweiligen Target erwarten.

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