Spectroscopic Characterization and Tissue Imaging Using Site-Selective Polyazacyclic Terbium(III) Chelates

Abstract

Polyazamacrocyclic chelates of terbium are shown to be useful in diagnostic medical imaging as tissue site-selective markers. Spectroscopic properties and biodistribution are studied for three terbium(III) species: 3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraaza-bicyclo[9.3.1]pentadeca-1(15),11,13-triene (abbreviated as PCTMB); 3,6,9-tris(methylene phosphonic acid)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(13),11,13-triene (abbreviated as PCTMP); and N,N'-bis(methylene phosphonic acid)-2,11-diaza [3.3]-(2,6)pyridinophane (abbreviated as BP2P). The respective aqueous molar absorptivities are found to be 3424, 2513, and 3281/2210 L mole−1 cm−1. Fluorescence quantum efficiency is determined against rhodamine 19 in basic ethanol and rhodamine 6G in ethanol. These values are 0.48, 0.21, and 0.40 for Tb-PCTMB, Tb-PCTMP, and Tb-BP2P, respectively. Biodistribution studies performed in Sprague–Dawley rats indicate tissue site-selectivity. Fluorescence images of bone tissues are presented and demonstrate the potential for using the lanthanide chelates to perform site-directed in vivo imaging for the early identification of abnormal tissue.

Chelating agents for radiolanthanides: Applications to imaging and therapy

“…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. 8).…”

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

“…[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).…”

Lanthanide Bimetallic Helicates forin VitroImaging and Sensing

“…The suitability of a lipid‐conjugated Tb III chelate as a membrane‐staining agent for morphological studies of Swiss albino mouse 3T3 cultured cells was also demonstrated 20 . In parallel, Bornhop and colleagues have developed high‐brightness Tb III labels for in vitro and in vivo analysis of abnormal tissues 13,21,22 . Finally, Parker and coworkers have designed Eu III complexes staining the nucleoli of live cell lines such as NIH 3T3, HeLa, and HDF 23,24 .…”