Ga-Labeled 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-bisphosphonate (BP))

Bisphosphonates (BPs; also known as diphosphonates), such as methylene diphosphonate (MDP) and zoledronic acid, can be labeled with technetium-99m ([Tc]-BPs) for use in bone scintigraphy to detect osteoporosis and other skeletal-related events (SREs), including bone metastases (1). These chemicals are known to promote osteoclast apoptosis and have a strong affinity for hydroxyapatite, a component of the bone matrix. The exact mechanism of action of these bone-seeking compounds is described in detail elsewhere (2-4). Although these labeled compounds have a high sensitivity, selectivity, and accuracy for the detection of SREs, they are known to generate some false positive and false negative results in the clinic (5). [F]-Fluoride is another nuclide that is commonly used for bone imaging with positron emission tomography (PET) and is believed to be superior to [Tc]-BPs for the diagnosis of SREs (6); however, the main limitations of using F are the high cost of production and the requirement of a cyclotron to produce it (5). In an effort to develop an imaging compound that does not have the limitations of tracers currently used to detect SREs with scintigraphy or PET, Suzuki et al. developed a bisphosphonate labeled with Ga, which has been shown to be potentially useful for the PET imaging of the skeletal system (5). The main advantage of using Ga (half-life = 68 min; β = 89%; E+ = 1.9 MeV) for bone imaging over either Tc (half-life = 6 h; γ = 100%; E+ = 140 keV) or F (half-life = ~110 min; β = 97%; E+ = 0.635 MeV) as a radiolabel is that Ga can be produced economically on-site with a Ge/Ga generator (5). Suzuki et al. coupled a BP with 1,4,7-triazacyclononane-1,4-7-triacetic acid (NOTA-BP) and labeled the product with Ga to obtain [Ga]-NOTA-BP (5). The investigators then compared the biodistribution of [Ga]-NOTA-BP with that of [Tc]-methylene diphosphonate ([Tc]-MDP) and [F]fluoride in rats. [Ga]-NOTA-BP was also evaluated for the imaging of osteolytic bone metastasis in mice.