Evans Blue Dye Derivatives for Serum Albumin Labeling

The invention is an imaging agent and method of use for imaging blood pools and the lymphatic system. The imaging agent binds with high affinity to serum albumin, the most abundant serum protein, and can be tagged with several isotopes making it suitable for magnetic resonance imaging or positron emission tomographic imaging. To date, only very few blood-pool tracers have been introduced for positron emission tomography. The existing ones have short half-lives (20.4 min for ¹¹C and 2.05 min for ¹⁵O) and thus can only be used in centers with an in-house cyclotron. Compared with these radiometals, ¹⁸F has the advantages of being a pure position emitter with ideal half-life. It is the dominant radioisotope used for PET imaging for both clinical applications and preclinical investigations. Evans blue dye has been an important tool in many physiological and clinical investigations because of its high affinity for plasma albumin and has been used for a long time in clinical practice for determination of patient plasma volume. By taking advantage of the high in-vivo EB binding affinity to albumin, the current imaging agent is a NOTA conjugate of truncated form of Evans blue (NEB) for in vivo albumin labeling and then labeling with ¹⁸F labeling by the formation of ¹⁸F-aluminum fluoride complex. The NOTA also facilitates radiometal labeling of NEB with either ⁶⁸Ga or ⁶⁴Cu. The resulting imaging agent does not affect the in vivo behavior of serum albumin such as circulation, extra-vascularization, and turn-over; thus the imaging results will reflect the distribution and metabolism of serum albumin accurately.