Andre Chatelain

Photodetection and photodynamic therapy of "early" squamous cell carcinomas of the pharynx, oesophagus and tracheo-bronchial tree

The efficacy of photodynamic therapy (PDT) alone was evaluated on 41 ‘early’ squamous cell carcinomas of the pharynx (10), oesophagus (15) and tracheo-bronchial tree (16). All lesions but two were synchronous second primaries in ENT-patients suffering from a more extensive cancer, governing the overall oncological prognosis.Photofrin I (3 mg/kg) or Photofrin II (2 mg/kg) were injected 72 h prior to the red light irradiation, supplied by an argon pumped dye laser. A diffusing cylinder was used to obtain a homogeneous light distribution at the tumour site (60 J to 150 J/cm2). In the oesophagus and bronchi, the results are good for cancers staged in situ or microinvasive at endoscopy (two recurrencies for 23 lesions treated). For more advanced cancers (submucosal in the oesophagus or invading the bronchial cartilage), the results are less satisfactory (three recurrencies for eight lesions treated). In the pharynx where light dosimetry is more difficult, the rate of recurrencies is higher (3/10 lesions treated). In the bronchi (one case) and oesophagus (one case), the longest disease-free survival is now 5 years.The irradiation of a non-cancerous zone of normal buccal mucosa on 25 patients having received HPD showed necrosis in all cases with light doses as low as 50mW/cm2 for 20 min (60 J cm−2), even with Photofrin II.We encountered six complications (three cicatricial stenosis, two fistulae, one severe sunburn), most of them resulting from the lack of selectivity of HPD. According to these experiments, PDT is efficient at destroying early squamous cell carcinomas in the pharynx, oesophagus and bronchi, but the tumour selectivity of HPD is poor in the digestive tract lined with squamous cell epithelium. The only hope for the future lies in the synthesis of a more selective and more stable photosensitizer. This discussion reviews possible directions of research for the development of new dyes (cationic dyes, dyes attached to monoclonal antibodies, etc), for PDT and hyperthermia, for photodetection of early cancers using a fluoro-endoscope, and finally, for tumour depth profiling in hollow organs using lasers of different wavelengths.

A fully sealed luminescent tube based on carbon nanotube field emission

A fully sealed luminescent tube of 40 cm length and 4 cm diameter based on carbon nanotube field emission is demonstrated. The device shows a homogeneous illumination over the whole length and circumference of the tube and reaches the luminance of conventional fluorescent tubes while being mercury-free, continuously dimmable and with a high illuminance capability. The realization has been made possible with the development of a chemical vapor deposition method to grow nanotubes homogeneously on long metallic wires, which provides an additional possibility to control the mean length and density of the emitters. This control has proven to be of utmost importance as it makes possible to adjust the emission voltage and emission site density needed to reach the target intensity and specifications of the device.

Photodetection of early cancer in the upper aerodigestive tract and the bronchi using photofrin II and colorectal adenocarcinoma with fluoresceinated monoclonal antibodies

The performance of a fluorescence endoscope for the detection of early cancer is clinically evaluated. the apparatus is based on the imaging of the laser-induced fluorescence (LIF) of a dye which localizes in the tumor after IV injection with a higher concentration than in the surrounding normal tissue. The tests are carried out in several of the hollow organs, such as the upper aerodigestive tract, the bronchi, and the colon. In the two former cases the dye used is photofrin II, whereas in the latter case conjugates between monoclonal antibodies (Mab) directed against carcinoembrionic antigen (CEA) and fluorescein molecules are injected. The fluorescence contrast between tumor and surrounding tissue is enhanced by real-time image processing which eliminates most of the tissue autofluorescence as well as the fluorescence due to the relatively small amount of dye localized in the normal tissue. This is done by recording the fluorescence image in two spectral domains, after which these two images are digitized and manipulated with a mathematical operator (lookup-table). The sources of false positives and false negatives are evaluated in terms of the fluorescent dye and tissue optical properties.

Clinical optical dose measurement for PDT: invasive and noninvasive techniques

Two methods for clinical optical light dosimetry are developed. In the first method, which is invasive, a fluorescent probe attached to an optical fiber is inserted by means of a thin hypodermic needle and measures light transmitted through the cheek as a function of the penetration depth. In the second noninvasive method, the diffusely reflected light intensity, from a small illuminated spot on the surface of the tissue to be investigated, is measured as a function of the radial distance along the surface. Preliminary results with both methods are presented. Simulations of the second measurements, which allow for a simplified extraction procedure of the relevant optical data from such measurements, are also shown.

Endoscopic tissue autofluorescence measurements in the upper aerodigestive tract and the bronchi

A single multimode optical fiber is used to excite and collect tissue autofluorescence as well as the fluorescence of an IV-injected fluorescent tumor marker. Measurements of the relative fluorescence intensity of a tumor marker as a function of the time after IV injection permit measurement of the kinetics of this substance in tumor, normal tissue, and skin. The authors believe that these are the first measurements of this kind in patients. Furthermore, the autofluorescence spectrum generated at several excitation wavelengths in different tissues is compared, for instance in the oesophagus, the bronchi, and the tongue. The measuring system is based on an optical multichannel analyzer which measures the fluorescence excited by monochromatic radiation from a spectrally filtered Xe lamp. A correlation between the observed pharmacokinetics and tumor properties like the degree of vascularization is of fundamental importance for each selected tumor marker. Also, the results of these measurements are used for the optical detection of tumors.

Clinical LIF pharmacokinetic measurements with Photofrin II for optimizing the photodetection of early cancer

New results are presented on the pharmacokinetics of the fluorescing fraction of Photofrin II in patients with an early cancer in the oesophagus or the buccal cavity. The light-induced fluorescence signal shows a relatively high contrast between tumor and surrounding normal tissue at short times after i.v. injection. The magnitude of this contrast appears to correlate with the staging of the cancer, the more invasive tumors showing the highest contrast. Some early results on the ex vivo fluorescence analysis of biopsies taken on patients injected with the new sensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC) demonstrate the selectivity of this efficient second generation photosensitizer for advanced lung cancer. mTHPC appears to have good properties for photodetection and has a rather high rate of photobleaching. The significant of the latter is discussed in relation to simplifying light application in PDT.