Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 May;80(5-6):744–755. doi: 10.1038/sj.bjc.6690418

Short- and long-term normal tissue damage with photodynamic therapy in pig trachea: a fluence-response pilot study comparing Photofrin and mTHPC

L H P Murrer 1, K M Hebeda 2, J P A Marijnissen 1, W M Star 1
PMCID: PMC2362296  PMID: 10360652

Abstract

The damage to normal pig bronchial mucosa caused by photodynamic therapy (PDT) using mTHPC and Photofrin as photosensitizers was evaluated. An endobronchial applicator was used to deliver the light with a linear diffuser and to measure the light fluence in situ. The applied fluences were varied, based on existing clinical protocols. A fluence finding experiment with short-term (1–2 days) response as an end point showed considerable damage to the mucosa with the use of Photofrin (fluences 50–275 J cm−2, drug dose 2 mg kg−1) with oedema and blood vessel damage as most important features. In the short-term mTHPC experiment the damage found was slight (fluences 12.5–50 J cm−2, drug dose 0.15 mg kg−1). For both sensitizers, atrophy and acute inflammation of the epithelium and the submucosal glands was observed. The damage was confined to the mucosa and submucosa leaving the cartilage intact. A long-term response experiment showed that fluences of 50 J cm−2 for mTHPC and 65 J cm−2 for Photofrin-treated animals caused damage that recovered within 14 days, with sporadic slight fibrosis and occasional inflammation of the submucosal glands. Limited data on the pharmacokinetics of mTHPC show that drug levels in the trachea are similar at 6 and 20 days post injection, indicating a broad time window for treatment. The importance of in situ light dosimetry was stressed by the inter-animal variations in fluence rate for comparable illumination conditions. © 1999 Cancer Research Campaign

Keywords: photodynamic therapy, light dosimetry, bronchus, Photofrin, mTHPC, normal tissue damage

Full Text

The Full Text of this article is available as a PDF (408.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrejevic S., Savary J. F., Monnier P., Fontolliet C., Braichotte D., Wagnières G., van den Bergh H. Measurements by fluorescence microscopy of the time-dependent distribution of meso-tetra-hydroxyphenylchlorin in healthy tissues and chemically induced "early" squamous cell carcinoma of the Syrian hamster cheek pouch. J Photochem Photobiol B. 1996 Nov;36(2):143–151. doi: 10.1016/s1011-1344(96)07362-9. [DOI] [PubMed] [Google Scholar]
  2. Cortese D. A., Edell E. S., Kinsey J. H. Photodynamic therapy for early stage squamous cell carcinoma of the lung. Mayo Clin Proc. 1997 Jul;72(7):595–602. doi: 10.1016/S0025-6196(11)63563-5. [DOI] [PubMed] [Google Scholar]
  3. D'Hallewin M. A., Baert L., Marijnissen J. P., Star W. M. Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder. J Urol. 1992 Oct;148(4):1152–1155. doi: 10.1016/s0022-5347(17)36846-5. [DOI] [PubMed] [Google Scholar]
  4. Hayata Y., Kato H., Konaka C., Hayashi N., Tahara M., Saito T., Ono J. Fiberoptic bronchoscopic photoradiation in experimentally induced canine lung cancer. Cancer. 1983 Jan 1;51(1):50–56. doi: 10.1002/1097-0142(19830101)51:1<50::aid-cncr2820510113>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  5. Lam S. Photodynamic therapy of lung cancer. Semin Oncol. 1994 Dec;21(6 Suppl 15):15–19. [PubMed] [Google Scholar]
  6. Lofgren L. A., Ronn A. M., Abramson A. L., Shikowitz M. J., Nouri M., Lee C. J., Batti J., Steinberg B. M. Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model. Arch Otolaryngol Head Neck Surg. 1994 Dec;120(12):1355–1362. doi: 10.1001/archotol.1994.01880360051010. [DOI] [PubMed] [Google Scholar]
  7. Marijnissen J. P., Baas P., Beek J. F., van Moll J. H., van Zandwijk N., Star W. M. Pilot study on light dosimetry for endobronchial photodynamic therapy. Photochem Photobiol. 1993 Jul;58(1):92–99. doi: 10.1111/j.1751-1097.1993.tb04908.x. [DOI] [PubMed] [Google Scholar]
  8. Marijnissen J. P., Star W. M. Calibration of isotropic light dosimetry probes based on scattering bulbs in clear media. Phys Med Biol. 1996 Jul;41(7):1191–1208. doi: 10.1088/0031-9155/41/7/008. [DOI] [PubMed] [Google Scholar]
  9. McCaughan J. S., Jr, Hawley P. C., Bethel B. H., Walker J. Photodynamic therapy of endobronchial malignancies. Cancer. 1988 Aug 15;62(4):691–701. doi: 10.1002/1097-0142(19880815)62:4<691::aid-cncr2820620408>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  10. Menezes da Silva F. A., Newman E. L. Time-dependent photodynamic damage to blood vessels: correlation with serum photosensitizer levels. Photochem Photobiol. 1995 Apr;61(4):414–416. doi: 10.1111/j.1751-1097.1995.tb08632.x. [DOI] [PubMed] [Google Scholar]
  11. Murrer L. H., Marijnissen H. P., Star W. M. Monte Carlo simulations for EndoBronchial Photodynamic Therapy: the influence of variations in optical and geometrical properties and of realistic and eccentric light sources. Lasers Surg Med. 1998;22(4):193–206. doi: 10.1002/(sici)1096-9101(1998)22:4<193::aid-lsm3>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  12. Murrer L. H., Marijnissen J. P., Star W. M. Ex vivo light dosimetry and Monte Carlo simulations for endobronchial photodynamic therapy. Phys Med Biol. 1995 Nov;40(11):1807–1817. doi: 10.1088/0031-9155/40/11/003. [DOI] [PubMed] [Google Scholar]
  13. Murrer L. H., Marijnissen J. P., Star W. M. Improvements in the design of linear diffusers for photodynamic therapy. Phys Med Biol. 1997 Jul;42(7):1461–1464. doi: 10.1088/0031-9155/42/7/018. [DOI] [PubMed] [Google Scholar]
  14. Murrer L. H., Marijnissen J. P., Star W. M. Light distribution by linear diffusing sources for photodynamic therapy. Phys Med Biol. 1996 Jun;41(6):951–961. doi: 10.1088/0031-9155/41/6/001. [DOI] [PubMed] [Google Scholar]
  15. Savary J. F., Monnier P., Fontolliet C., Mizeret J., Wagnières G., Braichotte D., van den Bergh H. Photodynamic therapy for early squamous cell carcinomas of the esophagus, bronchi, and mouth with m-tetra (hydroxyphenyl) chlorin. Arch Otolaryngol Head Neck Surg. 1997 Feb;123(2):162–168. doi: 10.1001/archotol.1997.01900020042006. [DOI] [PubMed] [Google Scholar]
  16. Wang Q., Altermatt H. J., Ris H. B., Reynolds B. E., Stewart J. C., Bonnett R., Lim C. K. Determination of 5,10,15,20-tetra-(m-hydroxyphenyl)chlorin in tissues by high performance liquid chromatography. Biomed Chromatogr. 1993 May-Jun;7(3):155–157. doi: 10.1002/bmc.1130070311. [DOI] [PubMed] [Google Scholar]
  17. Wilson B. D., Mang T. S., Stoll H., Jones C., Cooper M., Dougherty T. J. Photodynamic therapy for the treatment of basal cell carcinoma. Arch Dermatol. 1992 Dec;128(12):1597–1601. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES