Novel contrast agent targets early signs of breast cancer
Scientists in the US have synthesised a novel contrast agent to help spot early signs of breast cancer. Although only tested on pigs so far, the researchers hope the agent will lead to improved breast cancer screening and surgery in the future.
Mammography is the standard technique for breast cancer screening and uses low level x-rays to search for tumours or cysts. But mammography can miss the presence of microcalcifications - tiny deposits of calcium salts that form around cancerous tissue at an early stage of the disease.
Near-infrared (NIR) fluorescence mammography is a promising alternative. This technique requires an injection of contrast agent that selectively binds to microcalcifications, causing them to fluoresce under NIR light. NIR light penetrates well into living tissue without causing damage and is easy to detect.
’When used with optical tomography, doctors can reconstruct a three-dimensional image of tissues deep inside the breast, highlighting areas where tumours appear,’ explains Barbara Clough, who worked on the project.
Now, a team led by John Frangioni at the Beth Israel Deaconess Medical Center at Harvard Medical School, Massachusetts, have created Pam800, a contrast agent based on an osteoporosis drug called pamidronate.
Pamidronate is one of a family of drugs that contain a biphosphonate group, which preferentially binds to calcium salts. The pamidronate molecule contains a primary amine group, allowing an NIR fluorescent dye fragment to be easily attached via amide formation.
Until now this process has been very low yielding due to pamidronate’s extreme insolubility in organic solvents. The team solved this problem by protecting the pamidronate at an early stage with methyl ester groups, and then carefully removing them at the end of the synthesis, giving a 71 per cent overall yield.
When the researchers used Pam800 to look at pigs injected with calcium salt crystals, the found the could spot the soft-tissue embedded microcrystals with high sensitivity and, importantly, they could also distinguish between hydroxyapatite crystals - common in malignant breast cancer - and other crystals such as calcium oxalate, which are typically found in benign lesions.
Keith Paulsen, professor of biomedical engineering at the Thayer School of Engineering, New Hampshire, US, told Chemistry World: ’There is a lot of excitement about these techniques, and potential exists to find other contrast agents that target other diseases. The biggest problem is that getting approval for human trials takes a long time.’
et alAngewChem. Int. Ed., 2007, DOI: 10.1002/anie.200701216