Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer

In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pha...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 1999-07, Vol.71 (14), p.2607-2615
Main Authors: Bornhop, Darryl J, Hubbard, Darren S, Houlne, Michael P, Adair, Chris, Kiefer, Garry E, Pence, Barbara C, Morgan, David L
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cancer
Cell Survival
Chelating Agents
Humans
Investigative techniques, diagnostic techniques (general aspects)
Medical imaging
Medical sciences
Microscopy, Fluorescence
Miscellaneous. Technology
Neoplasms - diagnostic imaging
Neoplasms - pathology
Organometallic Compounds
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Radiography
Rats
Rats, Sprague-Dawley
Tumor Cells, Cultured
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Summary:In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (Δλ − 280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (Φ = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection.
ISSN:0003-2700
1520-6882
DOI:10.1021/ac981208u