In this paper we report the development of two attachments to a commercial cell phone that transform the phone's integrated lens and image sensor into a 350× microscope and visible-light spectrometer. The microscope is capable of transmission and polarized microscopy modes and is shown to have 1.5 micron resolution and a usable field-of-view of 150×150 with no image processing, and approximately 350×350 when post-processing is applied. The spectrometer has a 300 nm bandwidth with a limiting spectral resolution of close to 5 nm. We show applications of the devices to medically relevant problems. In the case of the microscope, we image both stained and unstained blood-smears showing the ability to acquire images of similar quality to commercial microscope platforms, thus allowing diagnosis of clinical pathologies. With the spectrometer we demonstrate acquisition of a white-light transmission spectrum through diffuse tissue as well as the acquisition of a fluorescence spectrum. We also envision the devices to have immediate relevance in the educational field.
Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.
The purpose of this review is to call attention in the use of chlorophyll-a and bacteriochlorophyll-a to develop more than 600 photosensitizers (lambda (max) 660 nm-800 nm) during the last 15 years (1990-2005) at the Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo. This article mainly includes the chemistry, preclinical results, and brief clinical data of some of the most effective photosensitizers. The utility of the tumor-avid photosensitizers in developing multimodality agents (imaging and therapy) is also presented.
Optical imaging has attracted a great attention for studying molecular recognitions because minute fluorescent tracers can be detected in homogeneous and heterogeneous media with existing laboratory instruments. In our preliminary study, a clinically relevant photosensitizer (HPPH, a chlorophyll-a analog) was linked with a cyanine dye (with required photophysical characteristics but limited tumor selectivity), and the resulting conjugate was found to be an efficient tumor imaging (fluorescence imaging) and photosensitizing agent. Compared to HPPH, the presence of the cyanine dye moiety in the conjugate produced a significantly higher uptake in tumor than skin. At a therapeutic/imaging dose, the conjugate did not show any significant skin phototoxicity, a major drawback associated with most of the porphyrin-based photosensitizers. These results suggest that tumor-avid porphyrin-based compounds can be used as "vehicles" to deliver the desired fluorescent agent(s) to tumor. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (fluorescence imaging and photodynamic therapy) provides the potential for tumor detection and targeted photodynamic therapy, combining two modalities into a single cost-effective "see and treat" approach.
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