Details

Autor(en) / Beteiligte

• Zha, Zhihao
• Wu, Zehui
• Choi, Seok Rye
• Ploessl, Karl
• Smith, Megan
• Alexoff, David
• Zhu, Lin
• Kung, Hank F

Titel

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

Ist Teil von

• Molecular pharmaceutics, 2020-05, Vol.17 (5), p.1674-1684

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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).