Fluorescence diagnostics

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The fluorescence diagnostics (FD), or photodynamic diagnostics (PDD) is a method for in vivo diagnosis of epithelial tumors and premalignant lesions .

Procedure

As in the photodynamic therapy a is (PDT) photosensitizer ( English photosensitizer ) or a precursor of a photosensitizing agent ( prodrug applied) that accumulates selectively in or on tumor cells. Exposure to light causes the sensitizer molecules to fluoresce. This fluorescent light can be detected by the naked eye or, better, by an optical system, and the tumor can thus be localized. Precancerous or cancerous changes show a significantly higher fluorescence due to the selective enrichment of the fluorophore in contrast to the benign changes.

Up to now, fluorescence diagnostics has been established primarily in dermatology and urology . In dermatology, this method is suitable for diagnosing non- melanoma tumors such as basal cell carcinomas or spinaliomas , but also of precancerous diseases such as actinic keratosis . In urology, fluorescence diagnostics is recommended by the European Association of Urology (EAU) in its guidelines for the diagnosis and treatment of urothelial carcinoma in situ . There are also promising approaches in the diagnosis of tumors in the mouth and throat, in the esophagus, stomach and intestines, and in gynecology in the early diagnosis of cervical cancer .

Structural formula of protoporphyrin IX.

Because of its high selectivity and good tolerability, protoporphyrin IX (PpIX) is almost exclusively used as a sensitizer in dermatology for FD . PpIX is formed after topical administration of 5-aminolevulinic acid (5-ALA) as a free acid or in the form of its methyl ester methyl 5-amino-4-oxopentanoate (MAOP) as part of heme biosynthesis. Since the porphyrins produced are endogenous substances, no side effects are known apart from the sensitization of the skin to light. The highest selective accumulation of PpIX in tumors is reached about 2 to 3 hours after topical application of MAOP.

Due to the absorption spectrum of porphyrins, light with a wavelength of 400 to 500 nm is used to excite the fluorescence (absorption maximum at approx. 405 nm) and the emitted fluorescence is between 600 and 750 nm (emission maximum at approx. 630 nm).

The detection of the emitted fluorescent light is possible without major technical aids, but it is associated with some disadvantages. The self-fluorescence of the skin (autofluorescence) can lead to an incorrect assessment of the fluorescence intensities. Another disadvantage is the need to darken the room during diagnostics. In comparison, the use of a CCD ( charge-coupled device ) based camera system offers significant advantages . The fluorescence images can be digitally post-processed and archived, and the self-fluorescence can be filtered out with the aid of suitable emission filters.

The detection depth, that is to say the depth up to which tumor cells can still be discovered, is fundamentally limited by the penetration depth of the dye and the penetration depth of the excitation light. The fluorescence of the ALA- or MAOP-induced porphyrins remains largely restricted to the epidermis .

Advantages of FD over other methods are the early diagnosis, which is also possible in hard-to-reach areas and in scarred or inflamed tissue, and the diagnosis without taking tissue samples.

literature

  • Dieter Jocham, Michael Landthaler, Rolf-Markus Szeimies: Clinical fluorescence diagnostics and photodynamic therapy. Thieme, Stuttgart 2nd edition 2004, ISBN 978-3131378323
  • Burkhard M. Lippert, S. Schmidt: Fluorescence diagnosis and photodynamic therapy. Shaker Verlag GmbH, 2000, ISBN 978-3826573934

Web links

Individual evidence

  1. ^ Ron R Allison, et al .: Photosensitizers in clinical PDT . (PDF) In: Elsevier (Ed.): Photodiagnosis and Photodynamic Therapy . 1, 2004, pp. 27-42. doi : 10.1016 / S1572-1000 (04) 00007-9 .
  2. ^ Clemens Fritsch, Thomas Ruzicka: Fluorescence Diagnosis and Photodynamic Therapy of Skin Diseases: Handbook and Atlas. Springer, Wien 1st ed. 2003, p. 23ff - E - Fluorescence Detection of ALA-induced Porphyrins (FDAP)
  3. ↑ CR Riedl: Fluoreszenzdiagnostik bei Urbladenkarzinom (PDF; 1.4 MB) Journal für Urologie und Urogynäkologie, special issue 6 (2003), p. 25
  4. ↑ Dieter Jocham, Herbert Stepp, Raphaela Waidelich: Photodynamic Diagnosis in Urology: State-of-the-Art (PDF) In: European Urology 53 (2008) 1138–1150
  5. ↑ Daniela Steinat: Evaluation of photodynamic diagnosis using 5-aminolevulinic acid in the basal cell carcinoma by 3D histology. Dissertation 2004, urn : nbn: de: bsz: 21-opus-15597 .
  6. ↑ M. Babjuk, W. Oosterlinck, R. Sylvester, E. Kaasinen, A. Böhle, J. Palou, M. Rouprêt: Guidelines on TaT1 (Non-muscle invasive) Bladder Cancer ( Memento of the original from March 22, 2011 in Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 136 kB) European Association of Urology 2010, pp. 6 - 5.9 Fluorescence cystoscopy @1@ 2Template: Webachiv / IABot / www.uroweb.org
  7. ↑ P.Schleier et al .: Possibilities and limits of fluorescence diagnostics and photodynamic therapy of oral carcinoma. In: German Dental Journal. 59 (2004) 5, pp. 276–283 ( PDF )
  8. ↑ Physikalisch-Technische Bundesanstalt (PTB): Working group 8.31: Tissue optics and molecular imaging - laser-assisted fluorescence diagnostics  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.ptb.de  
  9. ↑ H. Weisser, D. Meyer-Rogge, E. Meyer-Rogge: First experiences in private practice with a new topical photosensitizer MAOP for actinic keratoses and basaliomas. In: Akt Dermatol. Volume 30, 2004, pp. 306-311.
  10. ^ Clemens Fritsch, Thomas Ruzicka: Fluorescence Diagnosis and Photodynamic Therapy of Skin Diseases: Handbook and Atlas . 1st edition. Springer, Vienna 2003, ISBN 3-211-83827-9 , pp. 19 . (C - Light Used in FDAP and PDT, Fig. 24: Absorption spectrum of phorphyrin molecules )
  11. ↑ Daniela Steinat: Evaluation of photodynamic diagnosis using 5-aminolevulinic acid in the basal cell carcinoma by 3D histology. Dissertation 2004, p. 10 (Fig. 3: Scheme of the range of light through the skin), urn : nbn: de: bsz: 21-opus-15597 .