Daniel Braichotte

Clinical evaluation of a method for detecting superficial transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following topical application of 5-aminolevulinic acid: Preliminary results

In bladder cancer, conventional white light endoscopic examination of the bladder does not provide adequate information about the presence of “flat” urothelial lesions such as carcinoma in situ. In the present investigation, we examine a new technique for the photodetection of such lesions by the imaging of protoporphyrin IX (PpIX) fluorescence following topical application of 5‐aminolevulinic acid (ALA).

Clinical pharmacokinetic studies of photofrin by fluorescence spectroscopy in the oral cavity, the esophagus, and the bronchi

Background. To optimize photodynamic therapy (PDT) and photodetection of cancer, two important variables that must be considered are the uptake of the dye and the dye contrast between normal and neoplastic tissue after injection.

Clinical determination of tissue optical properties by endoscopic spatially resolved reflectometry

A noninvasive method to measure the optical properties of a diffusing and absorbing medium is described. Based on the spatially resolved measurement of diffuse reflectance at the sample surface, this method is particularly suitable for investigating the in vivo optical properties of biological tissues endoscopically in a clinical context. The sensitivity of the measurement is discussed, and two optical probes for two different clinical applications are presented. Preliminary measurements are performed on a nonbiological medium, which illustrate the possibilities of the proposed method. Finally, we report on in vivo measurements of the optical properties of the human esophageal wall at 630 nm.

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma

In a model of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of meta‐tetrahydroxyphenylchlorin (m‐THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I‐labeled photosensitizer, m‐THPC‐PEG gave on average a 2‐fold higher tumor uptake than free m‐THPC. In addition, at early times after injection, m‐THPC‐PEG showed a 2‐fold longer blood circulating half‐life and a 4‐fold lower liver uptake than free m‐THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m‐THPC‐PEG than for free m‐THPC at any time point studied from 2 to 96 hr post‐injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m‐THPC‐PEG was preferentially localized near the tumor vessels, whereas m‐THPC was more diffusely distributed inside the tumor tissue. To verify whether m‐THPC‐PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m‐THPC‐PEG was as potent as free m‐THPC in the induction of tumor regression provided that the irradiation dose for m‐THPC‐PEG conjugate was adapted to a well‐tolerated 2‐fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo. Int. J. Cancer 76:842–850, 1998.© 1998 Wiley‐Liss, Inc.

Optimizing light dosimetry in photodynamic therapy of early stage carcinomas of the esophagus using fluorescence spectroscopy

Under standardized conditions (drug and light dose, timing), the result of the photodynamic therapy (PDT) of carcinomas of the esophagus with tetra(meta‐hydroxy‐phenyl)chlorin (mTHPC) shows large variations between patients.

Clinical Evaluation of the Cutaneous Phototoxicity of 5,10,15,20-Tetra (m-hydroxyphenyl)chlorin

The cutaneous phototoxic reaction induced by intravenous injection of 5,‐10,‐15,‐20‐tetra(m‐hydroxyphenyl)chlorin (mTHPC) has been clinically evaluated in patients undergoing photodynamic therapy. These tests were performed on the backs of 23 patients with a solar simulator at various times after drug administration ranging from 5 h to 57 days. The mTHPC doses ranged from 0.1 to 0.3 mg/kg, and the illuminations lasted from 30 s up to 8 min. These tests have shown that the duration of the skin photosensitization induced after a typical therapeutic dose of mTHPC (0.15 mg/kg) is less important than with Photofrin®(2 mg/kg). The level of mTHPC in the skin was also assessed in vivo and at times corresponding to the irradiations using an optical fiber‐based spectrofiuorometer. This study indicates that the light‐induced fluorescence spectroscopy of mTHPC enables prediction of the degree of photosensitivity of the skin.

Light dosimetry for photodynamic therapy in the esophagus

Photodynamic therapy (PDT) is an efficient technique to treat superficial early cancers in the pharynx, esophagus, and tracheo‐bronchial tree. However, the lack of selectivity of some of the clinically used photosensitizers can result in significant damage to the healthy tissue during the treatment. In the esophagus, this may lead to medical complications such as stenosis and fistula. Insufficient selectivity may be compensated to some extent by accurate light dosimetry. Here, we present an approach to safer and more efficient PDT by improved light dosimetry in the esophagus.

In-vivo measurement of fluorescence bleaching of meso-tetra hydroxy phenyl chlorin (mTHPC) in the esophagus and the oral cavity

In vivo spectrofluorometric analysis during photodynamic therapy (PDT) is a tool to obtain information about fluorophore bleaching kinetics in tissue. Using a cylindrical esophageal light distributor for PDT with an integrated sensing fiber, together with a fluorescence detection setup, we can obtain tissue fluorescence spectra endoscopically in a clinical environment. This study was performed on patients with early squamous cell carcinomas in the esophagus. Patients were injected intravenously with 0.15 mg/kg of mTHPC and underwent PDT (lambda equals 514 nm, fluence rate equals 100 mW/cm2) 96 hours after injection. Bleaching kinetics of mTHPC and tissue autofluorescence at different wavelengths were recorded in real time and showed decreases in the observed fluorescence intensity in the 652 nm band of about 60% for light doses around 100 J/cm2. Additional information on bleaching kinetics induced at another excitation wavelength, lambda equals 652 nm, was obtained by irradiations at much lower doses in the buccal cavity. The data are analyzed using a simplified mechanism in which singlet oxygen is the hypothetical reactive intermediate which can both bleach the mTHPC and the autofluorescent molecules. The differential equations are solved by applying the quasi stationary state approximation for the reactive intermediate. The experimental data at least do not appear to contradict this oversimplified mechanism.

High-speed laser chemical vapor deposition of copper: a search for optimum conditions

The photothermal laser‐induced chemical vapor deposition of copper is studied as a function of the writing speed, the light intensity, and the diameter of the focal spot on the substrate, at three different pressures of the copperbishexafluoroacetylacetonate precursor. The height, the width, and the electrical conductivity of the deposited metal stripes are measured. The metalorganic vapor pressure is the key variable for attaining high writing speeds. Copper stripes have been obtained at 1 mm s−1 .

Growth rates and electrical conductivity of microscopic ohmic contacts fabricated by laser chemical vapor deposition of platinum

The laser chemical vapor deposition of platinum from its bishexafluoroacetylacetonate derivative is studied with a cw argon ion laser at 458 and 514 nm. The height, the width, as well as the electrical conductivity of the deposited stripes are reported as a function of the vapor pressure of the metalorganic precurser, the laser intensity, and the writing speed.