• Photosensitizer: Rhodamines
  • Tradename: TH9402
  • Company Photosensitizer: Theratechnologies
  • Clinical Application: Bone marrow purging
  • Wavelength (nm): 511
  • Extinction Coefficient (M-1 cm-1): 2.0 104
  • Mode of Delivery: Ex vivo
  • Delivery vehicle: Water-soluble
  • Typical Dose: 25 mM
  • Light Dose (J cm-2): 1–10
  • Time Post-Injection: n/a
  • Duration of Skin Photosensitivity: n/a

Because of their specific uptake by mitochondria and their known use as a fluorescent probe, rhodamines have been used extensively as photosensitizers[74].

This naturally led to their use as sensitizers in the treatment of malignant tumours. However, the readily available commercial dye, rhodamine 123, is a poor phototoxin because of its high fluorescence quantum yield[95]. This problem can be remedied by adding heavy atoms such as bromine or chlorine to the macrocycle. Known as the heavy atom effect, the addition of these atoms to the chromophore increases intersystem crossing from the singlet to the triplet state by increasing spin-orbital coupling, allowing otherwise forbidden changes in the spin state.

The addition of halogens to the chromophore also shifts the absorption maximum towards the red end of the spectrum. This is an important feature as rhodamines absorb light at approximately 500 nm, a wavelength where tissue penetration of light is minimal and every increase in wavelength represents an important increase in its tissue penetration[74]. Despite this, rhodamines have been shown to be very effective photosensitizers against malignant cells in vitro and Theratechnologies (Québec, Canada) has undertaken extensive preclinical studies to examine the ability of brominated rhodamine derivatives to eradicate of leukaemia cells from bone marrow extracts or mobilized peripheral blood stem cells for use in autologous transplantation[96].

Phase I clinical trials have begun using the brominated rhodamine analogue, TH9402, for the treatment of chronic myeloid leukaemia using the patented Photodynamic cell therapy process (PDP) as described on the company’s Internet site (http://www.theratech.com). This ex vivo photodynamic therapy, used for purging autologous stem cell grafts, has been shown to destroy diseased cells while sparing normal healthy cells, an important prerequisite for such a treatment protocol.