Presidential Greeting - American Society for Laser Medicine and ...

Harish Krishnamoorthi, Jonathan Cayce, Constantine Paras, Alex Makowski, Xiaohong Bi, Mark Mackanos, Duco
Jansen, Vanderbilt University, Nashville, TN; Lockheed-Martin Aculight, Bothel, WA
Background: Clinical diagnosis of malignant and benign skin lesions is often difficult because of the subjective
nature of visual inspection and the potential for sampling error in biopsy. Raman Spectroscopy has demonstrated
the potential to perform non-invasive classification of skin lesions; however, the high level of physiological and
anatomical variability in benign skin can complicate optical diagnosis. A thorough understanding of benign lesion’s
variability both between patients and within a single patient may lead to improved diagnostic outcomes. Study:
Here, we present a fiber-optic probe-based 785nm Raman Spectroscopy study of 164 patients with benign lesions,
which included seborrheic keratosis, actinic keratosis, basal cell carcinoma, squamous cell carcinoma, dysplastic
nevus, and congenital nevus. Measurements were made of both the lesions and adjacent or contralateral normal
skin. Diagnosis of the lesions was performed by dermatologists through visual inspection of patients prior to data
collection. Results: We report an analysis of the spectral variability of normal skin and common benign lesions.
Through a pairwise analysis, Raman Spectroscopy shows the ability to detect the presence of malignancy as well
as the potential to discriminate between benign tissue classes. Conclusion: Characterization of these classes of
skin is a critical first step in the formation of a non-malignant spectral database that will serve as the basis for future
comparisons with malignant lesions.
INTRAVITAL IMAGING OF ABNORMAL VASCULATURE IN PRENEOPLASTIC ORAL MUCOSA BY
TWO-PHOTON LUMINESCENCE OF GOLD NANORODS
Saam Motamedi, Tuya Shilagard, Kert Edward, Luke Koong, Suimin Qui, Gracie Vargas, University of Texas
Medical Branch, Galveston, TX
Background: Gold nanorods (GNRs) exhibit very bright two-photon luminescence (TPL) signals that have been
shown to be many times brighter than traditional fluorophores, They are of great interest as contrast agents for in
vivo optical imaging, such as in cancer, due to their ability to be excited with extremely low incident powers and
potential for enabling large imaging depths by intravital two-photon microscopy. The objective of the study was to
evaluate their use for visualizing abnormal microvasculature of oral precancerous lesions. Study: GNRs were
delivered i.v. into hamsters with DMBA-induced carcinogenesis on the buccal pouch. Intravital imaging by TPL was
performed immediately and 24 hours following injection on lesion sites first identified visually or by reflectance
imaging. Following the 24 hour timepoint, biopsies of imaged sites were obtained and processed for histological
staining by hemotoxylin and eosin. TPL images and 3D reconstructions were analyzed for vessel features, such as
tortuosity and blood vessel counts; histological sections were graded by a pathologist and counted for blood
vessels. Results: Low incident powers used for TPL of GNRs allowed for 3D visualization of lesion
microvasculature in vivo without confounding background autofluorescence. Intravital imaging within minutes of
intravenous delivery revealed an abnormal 3-dimensional vessel structure of dysplastic lesions, which were highly
dense and tortuous compared to vessels in normal oral mucosa, and revealed GNRs diffusely distributed
throughout lesion space after 24 hours. Conclusion: This investigation suggests that GNRs can function as
high-contrast imaging agents for visualization of in vivo features of carcinogenesis.
IN VIVO TUMOR-TARGETING OF GOLD NANOPARTICLES: EFFECT OF PARTICLE TYPE AND DOSING
STRATEGY
Priyaveena Puvanakrishnan, Jaesook Park, Parameshwaran Diagaradjane, Glenn Goodrich, Jon Schwartz, Sunil
Krishnan, James Tunnell, The University of Texas at Austin, Austin, TX; MD Anderson Cancer Center, Houston, TX;
Nanospectra Biosciences, Houston, TX
Background: Gold nanoparticles (GNP) have gained significant interest as nanovectors for combined imaging and
photothermal therapy of tumors. Delivered systemically, GNP’s preferentially accumulate at the tumor site via the
enhanced permeability and retention effect, and when irradiated with sufficient NIR light, produce sufficient heat to
treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a
function of the particle’s geometric properties (e.g. size and shape) and dosing strategy (e.g. number and amount of
injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor
targeting. Specifically, we investigated the tumor-targeting efficiency of pegylated gold nanoshells (GNS) and gold
nanorods (GNR) for single and multiple, fractionated dosing. Study: We used Swiss nu/nu mice with a
subcutaneous tumor xenograft model that received intravenous administration for a single and a fractionated dose
of GNS and GNR. We determined the GNP distribution and accumulation pattern within tumors using near-infrared
narrow-band imaging (NBI) and two-photon microscopy. We performed Neutron Activation Analysis (NAA) to
quantify the gold present in the tumor and liver. Results: NBI and two-photon microscopy of tumor xenografts
demonstrated a highly heterogeneous distribution of GNP within the tumor with higher accumulation at the cortex.
GNPs were observed in unique patterns surrounding the perivascular region. NAA results showed that the smaller
GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant
increase of GNS and GNR accumulation in liver for higher doses. However, multiple doses increased GNS only
slightly with no increase for GNR. Conclusion: These results suggest a significant effect of particle type on tumor
targeting ability; however, the effect of multiple doses on increasing particle accumulation appears minimal.