A New [⁶⁸Ga]Ga-HBED-CC-Bisphosphonate as a Bone Imaging Agent

Positron emission tomography (PET) imaging using ⁶⁸Ga-labeled bisphosphonates to target bone metastasis could be a valuable tool in cancer diagnosis and monitoring therapeutic treatment. A ⁶⁸Ga labeled ligand, N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) containing one bisphosphonate group (HBED-CC-BP, 1) was prepared and evaluated. The new ligand, 1, reacted rapidly to form [⁶⁸Ga]Ga-1, via complexing with [⁶⁸Ga]GaCl₃ eluted from a commercially available ⁶⁸Ge/⁶⁸Ga generator (in a sodium acetate buffer at pH 4, reaching >95% labeling yield at room temperature in 5 min). The resulting [⁶⁸Ga]Ga-1 showed excellent stability in vitro and in vivo. [⁶⁸Ga]Ga-1 displayed high binding affinity to hydroxyapatite and good uptake in the tibia and femur bone of normal mice. Biodistribution and MicroPET imaging studies of [⁶⁸Ga]Ga-1 in normal mice and rats showed excellent bone uptake and retention comparable to that of Na[¹⁸F]F. The results suggested that [⁶⁸Ga]Ga-1 might be suitable as a bone imaging agent in humans and it could be useful as a convenient alternative to the current bone imaging PET agent, Na[¹⁸F]F, without the need of a near-by cyclotron. Also, an automated synthesis module was developed to produce clinical doses of [⁶⁸Ga]Ga-1 in a consistent and reproducible manner. Currently, the investigation new drug application (IND) for [⁶⁸Ga]Ga-HBED-CC-BP, [⁶⁸Ga]Ga-1, has received FDA approval, and it is currently under clinical trial (IND #129870).