19 - Optical-Image-Guided Interventions
Meeting Room 4 10:00 - 12:00
|Chair(s): Chad Kanick, Scott C. Davis|
10:00 Optical Molecular Image-Guided Treatment of Residual Microscopic Tumors and Suppression of Multiple Treatment Escape Pathways BQ Spring*, Northeastern University
; RB Sears, Emmanuel College; LZ Zheng, Massachusetts General Hospital; Z Mai, Massachusetts General Hospital; R Watanabe, University of California San Diego; ME Sherwood, Massachusetts General Hospital; BW Pogue, Dartmouth College; SP Pereira, University College London; E Villa, University of California San Diego; T Hasan, Massachusetts General Hospital
Abstract: This talk will highlight two recent strategies guided by fluorescence molecular imaging for preventing tumor recurrence. The first enables selective photodestruction of residual deposits of microscopic tumors missed by conventional treatments that frequently seed local and distal recurrence using a unique antibody-conjugate that enables a combination of molecular targeting and cancer cell activation. This approach also facilitates visualization and monitoring of residual tumor deposits and their molecular expression profiles using fluorescence endomicroscopy. Second, we will present a newly developed nanoparticle drug delivery system motivated by molecular imaging of dynamic molecular signaling pathways associated with tumor regrowth and invasion. The nanoparticle supports photo-initiated release of multikinase inhibitors "at the right time and the right place" to suppress multiple modes of treatment escape. These new approaches support an expanded role for the use of image-guided photomedicine to suppress disease recurrence in the surgical bed and to reduce toxicities of molecular inhibitors and chemotherapy.
10:30 Quantitative Spectroscopy for Optical Monitoring of PDT D J Robinson*, Erasmus University Medical Center
Abstract: The use of reflectance and fluorescence spectroscopy for monitoring (pre-) clinical photodynamic therapy in has been under development for over 20 years. A large body of work has developed around the use of these types of optical measurements for monitoring patient individualised pharmacokinetics and in the application of PDT dosimetry. Metrics based on the measurement of photosensitiser content of tissue, the light fluence (rate), the presence of reactive oxygen species and the physiological response during and following PDT are being studied in pre-clinical models and some stage I/II clinical trials optimizing PDT. The application of quantitative spectroscopy is illustrated in 3 ongoing clinical studies utilizing topical PDT in the skin, intra-luminal PDT in the GI tract and interstitial PDT in the head and neck, and in a recent pre-clinical application of targeted-PDT for head and neck cancer. In these studies light fluence rate measurements are combined with reflectance and fluorescence spectroscopy to quantitatively determine changes in tissue physiology and photosensitiser content. Our results show that the photosensitiser under investigation has a critical influence on which parameters are most appropriately used to perform dosimetry. Changes in fluence rate during PDT were strongly influenced by changes in tissue optical properties caused by changes in light scattering coefficient, oxygenation and blood volume. These effects were fluence rate dependent and not always predictable. Monitoring fluorescence photobleaching during therapy and using this as a PDT dose metric is very challenging in an environment of changing tissue optical properties. In all cases the volume of interrogation of optical measurements is critical parameter particularly for interstitial PDT. We have found that truly quantitative measurements of photosensitiser fluorescence before PDT can predict the clinical response in some applications. The clinical implications of these types of measurements and future applications of imaging will be discussed.
11:00 All-Organic Nanovesicles for Multimodal PET/CT and Optical Fluorescence Assessment of Lymphatic Disseminations MS Valic*, University of Toronto and Princess Margaret Cancer Centre
; T Ye, University of Toronto and Princess Margaret Cancer Centre; C Zhang, University of Toronto and Princess Margaret Cancer Centre; W Jiang, Princess Margaret Cancer Centre; J Chen, Princess Margaret Cancer Centre; MQ Bernardini, University of Toronto and Princess Margaret Cancer Centre; G Zheng, University of Toronto and Princess Margaret Cancer Centre
Abstract: Cancer mortality is linked increasingly to early metastatic disease occult at the time of primary diagnosis. The detection of metastatic disease in the lymph nodes"”a common event in breast, colon, and cervical cancer"”has substantial clinical impact for prognosis and planning therapeutic strategies. However, identification of lymph node metastasis is problematic owing to varying sensitivity and specificity of non-invasive imaging techniques such as CT, MR, and PET. Recent advances in the development of "lympho-tropic" imaging agents to assess nodal disease have shown tremendous preclinical promise for non-invasive nodal characterization. One such agent is an all-organic unilamellar nanovesicle (Porphysome) with intrinsically activatable biophotonic properties. In addition to being biodegradable and biocompatible, Porphysomes can stably chelate radioactive copper-64 (Cu-64) to serve as a highly accurate PET imaging tool. Herein we describe the clinical development of radio-pharmaceutical Porphysome kits manufactured in accordance with current Good Manufacturing Practice (cGMP) and complying with United States Pharmacopeial (USP) standards for non-sterile pharmaceutical compounding. One-pot radio-labelling of single use Porphysome kits with copper-64 (II) chloride prepared parenteral injections of dose 5 mCi (185 MBq) with high radiochemical purity (> 95%). Intending to strengthen radio-labelled Porphysome signal accumulation and signal activation in lymph nodes in vivo, the physiochemical (size, surface charge and chemistry) and photobiological (fluorescence activation) properties of the Porphysome nanovesicles were optimized to promote measurable multi-modal signal enhancement in lymph nodes following parenteral administration. We anticipate these optimized "lympho-tropic" Porphysome kits will provide the desired signal selectivity and enhancement in lymph nodes burdened with metastatic disease in preclinical models with lymphatic dissemination.
11:30 IRDye® 700DX: A demonstration of structural stability and photodynamic principles with small molecule conjugates JL Kovar*, LI-COR Biosciences
; M Cradduck, LI-COR Biosciences; B Volcheck, LI-COR Biosciences; K Xing, LI-COR Biosciences; D Draney, LI-COR Biosciences; N Padhye, LI-COR Biosciences; T Urlacher, LI-COR Biosciences
Abstract: IRDye® 700DX (aka IR700) is a near-infrared phthalocyanine dye with structural attributes designed for photodynamic therapy (PDT) applications. Photolytic cleavage of Si-O-Si linkages of IRDye 700DX has been suggested as a factor in cell-killing. This effect was examined for the dye carboxylate at pH 4-8 using HPLC. IRDye 700DX fluorescence intensity was stable at pH levels >6 with no significant increase in degradation products such as structural loss of either axial arm or decrease in the dye concentration in the solutions. We demonstrate the principles of PDT apply to IRDye 700DX-labeled targeting agents such as small molecules. RGD, EGF, chlorotoxin (CLTX), and anti-EGFR Affibody® molecules were labeled and cells examined morphologically before and after irradiation with 690 nm light (32 J/cm^2). Reduced cell viability, a loss of mitochondrial potential, and an increase in Caspase 3/7 activity for RGD, EGF, and CLTX conjugates were noted at 20 h post-irradiation. IRDye 700DX exhibited a 4-fold increase in singlet oxygen production over non-dye controls with a significant reduction when sodium azide was added. IRDye 700DX production of reactive oxygen species, superoxide and hydroxyl radicals, was assessed using fluorogenic probes with and without specific scavengers for each radical. These data suggest cytotoxic effects, necrosis or apoptosis, may be dependent on the location of the probe at the time of light exposure, cell membrane versus intracellular. Taken together, these data support IRDye 700DX as a Type I and Type II photosensitizer that exhibits a high degree of photostability when undergoing PDT.