Clinical Trial Design and Development Work Group Within the Quantitative Imaging Network.

The Clinical Trial Design and Development Working Group within the Quantitative Imaging Network focuses on providing support for the development, validation, and harmonization of quantitative imaging (QI) methods and tools for use in cancer clinical trials. In the past 10 years, the Group has been working in several areas to identify challenges and opportunities in clinical trials involving QI and radiation oncology. The Group has been working with Quantitative Imaging Network members and the Quantitative Imaging Biomarkers Alliance leadership to develop guidelines for standardizing the reporting of quantitative imaging.

QIN Benchmarks for Clinical Translation of Quantitative Imaging Tools.

The Quantitative Imaging Network of the National Cancer Institute is in its 10th year of operation, and research teams within the network are developing and validating clinical decision support software tools to measure or predict the response of cancers to various therapies. As projects progress from development activities to validation of quantitative imaging tools and methods, it is important to evaluate the performance and clinical readiness of the tools before committing them to prospective clinical trials. A variety of tests, including special challenges and tool benchmarking, have been instituted within the network to prepare the quantitative imaging tools for service in clinical trials.

Photo activation of HPPH encapsulated in "Pocket" liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts.

We recently reported laser-triggered release of photosensitive compounds from liposomes containing dipalmitoylphosphatidylcholine (DPPC) and 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC). We hypothesized that the permeation of photoactivated compounds occurs through domains of enhanced fluidity in the liposome membrane and have thus called them "Pocket" liposomes. In this study we have encapsulated the red light activatable anticancer photodynamic therapy drug 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) (Ex/Em410/670 nm) together with calcein (Ex/Em490/517 nm) as a marker for drug release in Pocket liposomes.

Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway.

We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC), and 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC) carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave) laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm) but not calcein blue (Cal-B; Ex/Em 360/460 nm). In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways.

Novel applications of diagnostic X-rays in activating a clinical photodynamic drug: Photofrin II through X-ray induced visible luminescence from "rare-earth" formulated particles.

Introduction: In this communication we report on a novel non-invasive methodology in utilizing "soft" energy diagnostic X-rays to indirectly activate a photo-agent utilized in photodynamic therapy (PDT): Photofrin II (Photo II) through X-ray induced luminescence from Gadolinium Oxysulfide (20 micron dimension) particles doped with Terbium: Gd_{2}O_{2}S:Tb. Photodynamic agents such as Photo II utilized in PDT possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through (visible light) photon absorption, the agents exert their cellular cytotoxicity through type I and type II pathways through extensive generation of reactive oxygen species (ROS); namely, singlet oxygen ^{1}O_{2}, superoxide anion O_{2}^{-}, and hydrogen peroxide H_{2}O_{2}, within the intra-tumoral environment.

Fluorometric determination of the redox state and distribution of mitochondria in human malignant glioblastoma cells grown on different culturing substrates.

Objectives: To evaluate the redox state and the spatial distribution of mitochondria in malignant human brain cancer cells grown on different substrates.

Methods: Cellular autofluorescence images were obtained through an inverted fluorescence microscope and the redox fluorometric ratio was evaluated (after the subtraction of background) as the net fluorescence signal through the DAPI filter divided by the net fluorescence signal through the FITC filter. Spatial mitochondria distribution patterns were evaluated by division of the cell area at the midpoint between the nuclear and cell membranes.

Effect of low intensity laser interaction with human skin fibroblast cells using fiber-optic nano-probes.

Over the past forty years, many efforts have been devoted to study low power laser light interactions with biological systems. Some of the investigations were performed in-vitro, on bulk cell populations. Our present work was undertaken to apply specially engineered fiber-optic based nano-probes for the precise delivery of laser light on to a single cell and to observe production of low power laser light induced reactive oxygen species (ROS).

Combined shock-wave and immunogene therapy of mouse melanoma and renal carcinoma tumors.

The effects of ultrasonic shock waves (SW), recombinant interleukin-12 (rIL-12) protein and DNA plasmids coding for interleukin-12 (pIL-12) were investigated on progression of mouse B16 melanoma and RENCA renal carcinoma tumors. Tumor cells were implanted and grown on the hind legs of syngeneic mice. Before treatment, mice were anesthetized and the tumor region was shaved and depilated.