A team of researchers from the departments of medicine and radiology at Beth Israel Deaconess Medical Center in Boston have developed an optical contrast agent for near-infrared fluorescent imaging that shows promise for identifying hydroxyapatite (HA), a calcium salt found in breast microcalcifications as well as the osteoblasts of bone.
A study published in the Oct. 22 edition of Angewandte Chemie describes the scientists’ work in preparing the contrast agent for use in real-time image guidance for surgical applications requiring the visualization of bone or tissue calcification.
The group synthesized methylester-protected pamidronate, a HA-specific agent, conjoined with the fluorophore IRDye 800CW N-hydroxysuccinimide ester to create the contrast agent Pam800. The team then conducted pre-clinical studies of its performance in large-animal models systems approaching the size of humans.
They characterized the in-vivo performance of the compound during NIR image-guided surgery on Yorkshire pigs, whose organs are roughly the same size as humans. They found that intravenous administration of Pam800 provided high sensitivity detection of normal bones and was able to guide surgery before and after skin incision.
To test the agent’s applicability for breast cancer microcalcifications encountered during breast surgery, the researchers injected the models with HA and calcium oxalate crystals. Results of the experiment showed Pam800 detected the soft-tissue embedded HA crystals with high sensitivity and specificity.
“In particular, Pam800 correctly identified HA, which is common in malignant breast disease, but not calcium oxalate, which is typically deposited in benign lesions and is rarely seen in malignancies,” the authors wrote.