PDT has become a treatment of choice especially for the cases with multiple sites and large areas. However, the efficacy
of PDT is limited for thicker and deeper tumors. Depth and size information as well as vascularity can provide useful
information to clinicians for planning and evaluating PDT. High-resolution ultrasound and photoacoustic imaging can
provide information regarding skin structure and vascularity. We utilized combined ultrasound-photoacoustic
microscopy for imaging a basal cell carcinoma (BCC) tumor pre-PDT and the results indicate that combined ultrasound-photoacoustic
imaging can be useful tool for PDT planning by providing both structural and functional contrasts.
Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability
to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting
outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX
(PpIX) in phantoms and <i>in vivo</i>. We correct fluorescence against the effects of native tissue absorption and scattering
parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw
fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom
experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug
concentration <i>in vivo</i> at pre-PDT.
Protoporphyrin IX (PpIX) synthesized endogenously from 5-aminolevulinic acid (ALA), is effluxed from cells
expressing the ATP-dependent transporter ABCG2. Side population (SP) cells (named for their low red/blue
fluorescence distribution in flow cytometry plots with ABCG2 substrates such as Hoechst) are postulated to contain
cancer stem cells (CSC). The SP in U87 (human gliblastoma cell line) were more resistant to ALA-PDT than NON-SP
cells. Inhibiting ABCG2 activity with the tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) during incubation
with ALA increased PpIX in the SP by preventing its efflux and decreased the SP after subsequent PDT, enhancing
phototoxicity. Evasion of SP cells from ALA-PDT could cause tumor recurrence from CSC. Manipulation of ABCG2
levels on the SP with small molecule modulators may be a potential strategy for enhancing PDT by decreasing the
amount of substrate photosensitizer extruded from cells and lowering the threshold for phototoxicity.
Photodynamic Therapy (PDT) is emerging as a successful tool to treat both malignant and benign tumors. It involves the
interaction of a photosensitizer which upon activation by the appropriate light dose, leads to a cytotoxic and vasculotoxic
photodynamic reaction. Improvements in PDT in areas such as the delivery and selectivity of photosensitizers,
light-delivery and overall efficacy have helped to increase its attractiveness as an option for therapy. For optimizing the
PDT treatment by a "see and treat approach," we have developed a number of tumor avid photosensitizers (PS) namely
HPPH-Cyanine dye conjugates or other compounds (Iodinated photosensitizers) which have the ability for Optical and/or
PET imaging as well as being effective photosensitizers for treatment. Hyperthermia refers to various techniques of heat
application which may be delivered as a single modality or as part of an adjunct treatment option to the existing cancer
therapies. Depending upon the temperature range used, hyperthermia might either directly induce cell kill or enhance the
efficacy of other treatment modalities. Hyperthermia increases blood flow within the body, which may allow for higher
dose delivery of photosensitizers with subsequent increased therapeutic efficacy of PDT. Hyperthermia could also
increase the sensitivity of molecular imaging. The use of multifunctional photosensitizers for imaging and PDT is an
emerging area and we have developed a few such agents in our lab. We wish to explore the use of hyperthermia to
improve the use of such multifunctional photosensitizers from the point of view of imaging and/or therapy.
Hyperthermia can be performed either as a whole-body mode or as localized mode. Our goal is to see which of the two
heating modalities offers us better outcome.
Various problems arising during molecular imaging of different fluoroprobes and metabolites used in PDT can be
circumvented by focusing on multifunctional therapy agents. Thus an effective photo sensitizer coupled with other
useful roles to play in PDT treatment make nanoparticles as a good vehicle for different delivery assuming
multifunctional roles not only in PDT but also as therapeutic agents for targeted delivery. A new approach is the
involving use of 100 nm NPs as photo sensitizers and/or imaging agents. In our Lab., we employ two such NPs and are
ORMOSIL (organically Modified Silica) and PAA (Polyacrylamide) which are found to be biologically very safe
without disturbing the therapeutic value. The size of the nanoparticles determined by TEM and Dynamic Light
Scattering are ~30 nm. These NPs are taken up in conjunction with cyanine dye at near infra red as it has been reported
in literature that encapsulated NPs shows very low singlet oxygen production compared with the post-loaded NPs though
the reasons are not yet clear. Therefore, we investigated the idea of post-loading or adsorbing vis-a-vis encapsulation.