Publication

Photoimmunodiagnosis with antibody-fluorescein conjugates: In vitro and in vivo preclinical studies

Abstract

The use of dyes has been helpful for the photodiagnosis of small cancers accessible to endoscopic examn. An important limiting factor of this technol. is that the presently used fluorescent dye mixt. has a relatively poor capacity to accumulate preferentially in malignant tissue and a low quantum yield of fluorescence. To improve these parameters, fluorescein was coupled to an anti-carcinoembryonic antigen (CEA) MAb and the biodistribution of several conjugates was studied in nude mice bearing a human colon carcinoma xenograft. In vitro, such conjugates with fluorescein to MAb molar ratios ranging 4-19, trace labeled with 125I, showed >82% binding to insolubilized CEA. However, since the aim of this work was the evaluation of MAb-dye conjugates designed for in vivo tumor localization, all newly prepd. MAb-fluorescein conjugates were tested in the exptl. model of nude mice bearing CEA expressing human colon carcinoma xenografts. Under these exptl. in vivo conditions, the conjugate contg. 10 fluorescein mols. per MAb mol. gave an excellent tumor localization (up to 30% of the injected dose per g tumor at 24 h), whereas a conjugate with 19 fluorescein mols. per MAb mol. gave almost no in vivo localization in the tumor, probably due to a very short half-life. Tumor-to-liver, -kidney, and -muscle ratios of 20, 30, and 72, resp., were obtained at 48 h after injection of the conjugate contg. 10 fluorescein mols. per MAb mol. In the spectrofluorometric anal., a high fluorescence intensity was obsd. in the tumor after injection of the anti-CEA MAb conjugate. To compare these results with a conventionally used dye, mice bearing the same xenografts received a purified form of hematoporphyrin, Photofrin II. The intensity of the fluorescence signal of the tumor after an injection of 0.44 mg fluorescein coupled to 20 mg of MAb was 8-fold higher than that obtained after injection of 60 mg of Photofrin II. These results illustrate the possibility of improving the specificity of in vivo tumor localization of dyes for laser-induced fluorescence photodetection and phototherapy by coupling them to MAb directed against tumor markers.

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Ontological neighbourhood
Related concepts (32)
Tumor marker
A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer. An elevated level of a tumor marker can indicate cancer; however, there can also be other causes of the elevation (false positive values). Tumor markers can be produced directly by the tumor or by non-tumor cells as a response to the presence of a tumor.
Neuroendocrine tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body. Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, including a similar histological appearance, having special secretory granules, and often producing biogenic amines and polypeptide hormones.
Fluorescein
Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used as a fluorescent tracer for many applications. The color of its aqueous solutions is green by reflection and orange by transmission (its spectral properties are dependent on pH of the solution), as can be noticed in bubble levels, for example, in which fluorescein is added as a colorant to the alcohol filling the tube in order to increase the visibility of the air bubble contained within.
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