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