Download high-res image (112KB)Download full-size image

Two new DTPA analogues, centrally (L1) and terminally (L2) functionalised with a 1,8-naphthalimide chromophore, have been successfully prepared and fully characterized. Their Gd(III) complexes have also been prepared and evaluated for their ability to act as dual modal contrast agents (MRI/OI). The highly reproducible R1 relaxivity of L1 (8.10 ± 0.21 mM−1 s−1, 25 °C and 30 MHz) is markedly higher than other DTPA based contrast agents. The Gd(III) complexes of both L1 and L2 have been evaluated as luminescence probes; the ligand based fluorescence is not quenched upon complexation.

Two new DTPA analogues, centrally (L1) and terminally (L2) functionalised with a 1,8-naphthalimide chromophore, have been successfully prepared and fully characterized. Their Gd(III) complexes have also been prepared and evaluated for their ability to act as dual modal contrast agents (MRI/OI). The highly reproducible R1 relaxivity of L1 (8.10 ± 0.21 mM−1 s−1, 25 °C and 30 MHz) is markedly higher than other DTPA based contrast agents. The Gd(III) complexes of both L1 and L2 have been evaluated as luminescence probes; the ligand based fluorescence is not quenched upon complexation.

Trivalent lanthanide ions offer remarkable opportunities in the design of bioimaging agents: this review presents an accessible discussion of their application in both optical and magnetic resonance imaging. Aspects of molecular design, control over key physical properties and biological compatibility are discussed in this context, together with developments and opportunities as responsive probes and in multimodal imaging.

The radiometal 64Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for 64Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(II) and co-ordinates via a trigonal bipyramidal N4S array of donor atoms. Promisingly, cell uptake studies revealed that 64Cu-MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high CuII/I redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of 64Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent 64Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than 64Cu-MTUBo.

Trivalent lanthanide ions offer remarkable opportunities in the design of bioimaging agents: this review presents an accessible discussion of their application in both optical and magnetic resonance imaging. Aspects of molecular design, control over key physical properties and biological compatibility are discussed in this context, together with developments and opportunities as responsive probes and in multimodal imaging.

The radiometal 64Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for 64Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(II) and co-ordinates via a trigonal bipyramidal N4S array of donor atoms. Promisingly, cell uptake studies revealed that 64Cu-MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high CuII/I redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of 64Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent 64Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than 64Cu-MTUBo.