Biomedical Engineering Reference
In-Depth Information
patient or lesion. The various dosimetry methods outlined above could im-
prove this situation, but they are rarely used in routine clinical practice at
this time, in part because they are still rather complicated to use and inter-
pret. A major technical challenge is to devise the next generation of dosimetry
devices that will be simple and fast to use, minimally invasive, inexpensive,
and reliable. Until this happens, PDT will continue to evolve largely as an
empirical procedure with optimization based on dose ranging in clinical tri-
als.
A second issue is the continuing high cost of light sources. Using existing
technologies it is not clear how this can be significantly reduced. Certainly,
part of the cost comes from dealing with medical devices where significant
investments are required to ensure safety and reliability. It is becoming clear
that, for some potentially important applications, it is the cost of the light
source that is limiting, not the cost of the photosensitizer. Hence, there are
significant opportunities for optical engineers and physicists to devise new
devices.
A further major limitation is that the specificity of photosensitizer target-
ing of disease has not been high enough to use unlimited light safely. Attempts
have been made to improve this, for example, by linking the photosensitizer
to antibodies to target tumors cells, but these have not been particularly suc-
cessful to date. PDT beacons could change this significantly. However, it will
be challenging to get these into clinical trials and then through regulatory
approvals, so that the preclinical results in vivo will have to be outstanding
to make the effort worthwhile.
With respect to tissue response monitoring, there are many novel biopho-
tonic imaging and spectroscopic techniques being developed for other appli-
cations that could also be valuable in PDT: fluorescence imaging is a prime
example, while others include Raman spectroscopy (to report biochemical
changes) and intravital second harmonic generation imaging (changes in tis-
sue architecture). PDT monitoring will not drive the development of these
techniques but will benefit from them.
Three other major aspects of PDT are worth mentioning:
- The parallel development of “photodynamic diagnostics,” particularly for
tumor detection and localization [23]
- The combination of PDT with other therapeutic modalities, e.g., (fluo-
rescence guided) tumor resection followed by PDT to eliminate residual
minimal disease
- The extension of PDT into new applications, particularly to modify cells
or tissue function rather than destroying them: recent examples are for
modifying bone growth and for targeting epilepsy.
In addition to these clinical applications, the principle of light-activated
drugs may also be useful for basic life sciences research. One example is the use
of 2
γ
PDT to uncage growth factors in order to direct the growth of neurons
in tissue engineering [31].
