MTCT: MRI, NMR detect early cancer treatment response
BOSTON--Novel targeted cancer therapies could benefit from nuclear MR (NMR) and spectroscopy imaging to obtain an early indication of drug efficacy and guide personalized medicine, according to a presentation Tuesday at the Molecular Targets and Cancer Therapeutics (MTCT) conference.
Kevin M. Brindle, PhD, professor of biochemistry at the University of Cambridge in England, said that monitoring tumor cell death was an indicator of a drug working very early during treatment long before there is any evidence of tumor shrinkage.
Brindle and his colleagues are developing a targeted contrast agent that allows detection of apoptotic cells by NMR.
“We showed that the C2A domain of the protein synaptotagmin would bind to the phosphatidylserine that appears on the surface of apoptotic cells. When conjugated to small paramagnetic iron oxide particles, this protein allowed MRI detection of apoptotic cells in a tumor treated with chemotherapeutic drugs,” Brindle said.
Altered water diffusion can also serve as an early biomarker of therapeutic efficacy. The technique is relatively sensitive and has been translated to the clinic, Brindle noted.
Hyperpolarized 13C-labeled metabolites can increase sensitivity in NMR and help in detecting tumor cell death through changes in tumor cell metabolism. The researchers have shown that the exchange of hyperpolarized 13C-label between the carboxyl groups of lactate and pyruvate could be imaged in tumors, and that this flux was decreased in treated tumors undergoing drug-induced cell death.
Similarly, hyperpolarized 13C-fumarate can be used to monitor necrotic cell death; hyperpolarized 13C-glutamine activity can be correlated with the rate of cellular proliferation and could be used to detect the early responses of tumors to cytotoxic and cytostatic drugs.
Brindle concluded that there are several markers of cell death that can be detected using NMR and spectroscopy. These methods are valuable in oncology and could be used in drug development to obtain an early indication of efficacy and then later guide patient treatment, he said.
Kevin M. Brindle, PhD, professor of biochemistry at the University of Cambridge in England, said that monitoring tumor cell death was an indicator of a drug working very early during treatment long before there is any evidence of tumor shrinkage.
Brindle and his colleagues are developing a targeted contrast agent that allows detection of apoptotic cells by NMR.
“We showed that the C2A domain of the protein synaptotagmin would bind to the phosphatidylserine that appears on the surface of apoptotic cells. When conjugated to small paramagnetic iron oxide particles, this protein allowed MRI detection of apoptotic cells in a tumor treated with chemotherapeutic drugs,” Brindle said.
Altered water diffusion can also serve as an early biomarker of therapeutic efficacy. The technique is relatively sensitive and has been translated to the clinic, Brindle noted.
Hyperpolarized 13C-labeled metabolites can increase sensitivity in NMR and help in detecting tumor cell death through changes in tumor cell metabolism. The researchers have shown that the exchange of hyperpolarized 13C-label between the carboxyl groups of lactate and pyruvate could be imaged in tumors, and that this flux was decreased in treated tumors undergoing drug-induced cell death.
Similarly, hyperpolarized 13C-fumarate can be used to monitor necrotic cell death; hyperpolarized 13C-glutamine activity can be correlated with the rate of cellular proliferation and could be used to detect the early responses of tumors to cytotoxic and cytostatic drugs.
Brindle concluded that there are several markers of cell death that can be detected using NMR and spectroscopy. These methods are valuable in oncology and could be used in drug development to obtain an early indication of efficacy and then later guide patient treatment, he said.