Jonathan Marmurek1,2, Khaled Nasr3, Elena Vinogradov2, Ananth J. Madhuranthakam4, John V. Frangioni3, Robert E. Lenkinski2
1Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA, USA; 2Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 3Hematology & Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 4Global Applied Science Laboratory, GE Healthcare, Boston, MA, USA
We present a high-relaxivity gadolinium-bisphosphonate contrast agent that specifically targets hydroxyapatite, the malignant form of breast cancer microcalcification. The effect of increasing contrast agent concentration on longitudinal relaxation times measured by ultra-short echo time imaging was consistent with a Langmuir adsorption isotherm. High-affinity binding of the bisphosphonate ligand to hydroxyapatite restricts the rotational freedom of the adsorbed contrast agent and results in an apparent relaxivity exceeding 1000 s-1/mM. This enhancement enables the detection of bound contrast agent at concentrations as low as 1 μM.