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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Veröffentlicht in:Analytical chemistry (Washington) 1999-07, Vol.71 (14), p.2607-2615
Hauptverfasser: Bornhop, Darryl J, Hubbard, Darren S, Houlne, Michael P, Adair, Chris, Kiefer, Garry E, Pence, Barbara C, Morgan, David L
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container_end_page 2615
container_issue 14
container_start_page 2607
container_title Analytical chemistry (Washington)
container_volume 71
creator Bornhop, Darryl J
Hubbard, Darren S
Houlne, Michael P
Adair, Chris
Kiefer, Garry E
Pence, Barbara C
Morgan, David L
description 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.
doi_str_mv 10.1021/ac981208u
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source ACS Publications; MEDLINE
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
title Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer
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