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

Abstract

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 (delta lambda--280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (phi = 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.

Chelating agents for radiolanthanides: Applications to imaging and therapy

“…8). The luminescent Tb(III) complexes possess high quantum yields 72 and supporting studies reported the use of 153 Sm complexes which showed localisation in bone tissue of rats. 73 It is noteworthy that related coordination chemistry with 90 Y has been reported with PCTMB (Fig.…”

A Versatile Ditopic Ligand System for Sensitizing the Luminescence of Bimetallic Lanthanide Bio‐Imaging Probes

“…Keywords: helical structures · heterometallic complexes · imaging agents · lanthanides · luminescence dine-based cryptands, [16] cyclen derivatives containing coordinating and sensitizing groups, [17] aza-macrocycles incorporating a pyridine, bipyridine or terpyridine unit [18,19] and b-diketonates [20] ), which often have in common the simultaneous use of carboxylate (or amide) and amine coordinating groups.…”

“…[25] Tb III -based chelates have also proved useful, as exemplified by a lipid-conjugated chelate that functions as a membrane-staining agent in morphological studies of Swiss albino mouse 3T3 cultured cells, [22] or by Bornhops high brightness macrocyclic labels for in vitro and in vivo analysis of abnormal tissues. [18,26,27] More recently, Parker and co-workers have designed Eu III complexes that specifically stain the nucleoli of several cell lines (CHO, COS, NIH 3T3, HeLa, and HDF). [15,[28][29][30] Most lanthanide ions are also paramagnetic and possess an anisotropic susceptibility tensor that makes them useful for the structural investigation of axial complexes [31] or proteins [32] by NMR spectroscopy, while Gd III has emerged as a universal contrast agent for 3D imaging of biological structures (MRI).…”

Breast Cancer Detection Using Optical Vascular Fusion

“…14,21-24 Several research groups are examining the use of contrast agents for breast cancer detection. [24][25][26][27][28] Others have performed animal studies using window chambers to provide direct optical access to study the microenvironment of a tumor. 29,30 A number of ex vivo studies of the optical properties of normal and diseased breast tissue have also been performed.…”