Biomedical subjects

Suzanne V Smith

Publications and source records attributed to Suzanne V Smith.

6 recordsLinked to original sources

PubMed2006

New 64Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr.

The success of positron emission tomography (PET) in personalised medicine and drug development requires radioisotopes that provide high quality images and flexible chemistry for a broad application. 64Cu is arguably one of the most suitable PET isotopes for imaging with the evolving target agents, but there are not many appropriate chelating agents for 64Cu and this has limited its wider application. The bi-functional chelator, SarAr is known to bind 64Cu2+ quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10(-6) M over a range of pH (4-9). In this paper the conjugation of SarAr to the whole and fragmented antibody is described. Conjugation of the SarAr to the protein does not impair its coordination of the 64Cu. It complexes the 64Cu2+ rapidly, quantitatively and essentially irreversibly at pH 5. Animal studies show that the 64Cu-SarAr-immunoconjugates maintain their specificity for the target and are stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit formulation and is readily adaptable for the wider application in 64Cu PET imaging.

Animals↗

PubMed2005

Technology evaluation: huN901-DM1, ImmunoGen.

ImmunoGen is developing huN901-DMI, a compound comprised of a CD56-targeted humanized N901 antibody conjugated to the company's proprietary cytotoxic agent. DM1, using its tumor-activated prodrug technology, for the potential treatment of cancers that express CD56, in particular, small-cell lung cancer.

Ado-Trastuzumab Emtansine↗

PubMed2005

Challenges and opportunities for positron-emission tomography in personalized medicine.

Of the non-invasive functional imaging tools available, positron-emission tomography (PET) is generally expected to have the greatest potential for delivering the vision of personalized medicine. This can be achieved by the production of designer PET probes with exquisite sensitivity that can profile key biological processes that are specific to a disease. However, the challenge for the PET field will be its capability to produce and supply cost-effective PET probes to the wider community. This will most likely be achieved through the provision of long-lived PET radioisotopes with imaging qualities that match the performance of the evolving PET camera technology and chemistry that is amenable to kit formulations. Additionally, of the emerging PET radiotracers, (64)Cu has the optimum chemistry and emission characteristics for the wider application of PET in personalized medicine.

Copper Radioisotopes↗

PubMed2004

Molecular imaging with copper-64.

Molecular imaging is expected to change the face of drug discovery and development. The ability to link imaging to biology for guiding therapy should improve the rate at which novel imaging technologies, probes, contrast agents, drugs and drug delivery systems can be transferred into clinical practice. Nuclear medicine imaging, in particular, positron emission tomography (PET) allows the detection and monitoring of a variety of biological and pathophysiological processes, at tracer quantities of the radiolabelled target agents, and at doses free from pharmacological effects. In the field of drug discovery and development, the use of radiotracers for radiolabelling target agents has now become one of the essential tools in identifying, screening and development of new target agents. In this regard, (64)Cu (t(1/2)=12.7 h) has been identified as an emerging PET isotope. Its half-life is sufficiently long for radiolabelling a range of target agents and its ease of production and adaptable chemistry make it an excellent radioisotope for use in molecular imaging. This review describes recent advances, in the routes of (64)Cu production, design and application of bi-functional ligands for use in radiolabelling with (64/67)Cu(2+), and their significance and anticipated impact on the field of molecular imaging and drug development.

Contrast Media↗

PubMed2004

Technology evaluation: cantuzumab mertansine, ImmunoGen.

ImmunoGen is developing cantuzumab mertansine, in which the CanAg antigen-targeted humanized antibody C242 is conjugated to the company's proprietary cytotoxic agent, DM1, using ImmunoGen's tumor-activated prodrug technology. Cantuzumab mertansine is undergoing phase II trials for the potential treatment of CanAg-expressing cancers, including pancreatic and colorectal cancers and non-small-cell lung cancer.

Animals↗

PubMed2003

Insights into the mechanisms of copper tolerance of a population of black-banded rainbowfish (Melanotaenia nigrans) (Richardson) exposed to mine leachate, using 64/67Cu.

This study investigates the mechanisms of copper tolerance of a population of black-banded rainbowfish (Melanotaenia nigrans) (Richardson). The population has been exposed to elevated copper concentrations for over 40 years, due to leachate from the Rum Jungle uranium/copper mine. At the time of collection the 96 h EC(50) of exposed [E] fish was 8.3 times higher than that of reference [R] fish. The bioconcentration of 64/67Cu in fish was used to investigate the mechanism of copper tolerance in E fish. Both E and R fish were exposed to low (L(Cu), 30 microg Cu l(-1)) and elevated (E(Cu), 300 microg Cu l(-1)) copper concentrations for 24 and 48 h, respectively. Radioactivity was measured at seven or eight time points in four tissue sections: head (including gills, heart and brain), internal organs (including gastrointestinal tract, liver, kidneys and gonads), muscle and whole body. One-compartment bioconcentration models were fit to data and compared using an F-test. Copper concentrations in all tissue sections were significantly (P<0.05) less (up to 50%) in E fish compared with the respective tissue sections of R fish when exposed to both L(Cu) and E(Cu). The exception was copper accumulation in the internal organs, which was not significantly different between E and R fish exposed to E(Cu). The mechanism of copper tolerance was concluded to be reduced copper uptake in the gills, rather than increased binding or elimination. Allozyme electrophoresis was performed to determine if genetic selection had occurred in the E fish population. Allozyme frequencies at the AAT-1 and GPI-1 loci were significantly (P<0.05) different between E and R fish. Heterozygosity was reduced in E fish compared with that of R fish. Collectively these results suggest that genetic selection may have occurred in the E fish population. Consequently, the selection of allozymes less sensitive to copper may be another mechanism of copper tolerance of E fish. This is the first study on the mechanisms of copper tolerance in a wild fish population that has been exposed to elevated copper concentrations. These findings aid the understanding of metal tolerance in fish and emphasise the importance of sample selection and its implication for toxicity testing.

Adaptation, Physiological↗