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lüll (99m)Tc/(188)Re-Labeled dipicolylamine-alendronate Chopra AMolecular Imaging and Contrast Agent Database (MICAD)-/-ä 2004[]; ä (ä): äBisphosphonates (BPs) or nitrogen-containing bisphosphonates (NBP) are often used for the management of pain palliation and disorders related to skeletal tissue, including those arising from cancer metastases, because these compounds exhibit a very high affinity for hydroxyapatite (HA), a component of the bone matrix. These phosphonates tend to accumulate in osteoclasts at areas of increased bone metabolism by inhibiting the farnesyl diphosphate synthase, an important enzyme of the mevalonate pathway in the cell (1), as described by Drake et. al. (2). Several BPs and NBPs are available commercially for clinical use to treat different bone disorders, and there are ongoing clinical trials approved by the United States Food and Drug Administration to evaluate these compounds for the treatment of various bone ailments. In addition, BPs are often labeled with (99m)Tc or (186/188)Re and used for the imaging and treatment of bone metastases. However, these compounds have limitations primarily because they exist either as a mixture of anionic compounds with varying properties (e.g., (99m)Tc-labeled methyl diphosphonate (MDP)) or are rapidly degraded (e.g., [(186/188)Re]MDP) under in vivo conditions, resulting in a reduced uptake at targeted bone areas and an increased accumulation in non-target soft tissue (3). The (99m)Tc- or (186/188)Re-labeled BPs were suggested to have these limitations because the compounds possess dual activities: one phosphonate group of the BP molecule acts as a radionuclide chelator, and the other phosphonate group binds to the target(s). Therefore, due to the close proximity of the two groups, one activity may be interfering with the other (3). To circumvent problems associated with the radiolabeled BPs, investigators developed NBPs with two independent activities such that the nitrogen-containing part would only chelate the radiotracer and the BP part would target the bone (4, 5). These NBPs are produced by complex synthetic procedures, are usually obtained as enantomeric mixtures, and bind to plasma proteins (3). In an effort to produce a NBP that does not have these limitations, Torres Martin de Rosales et al. synthesized an easy-to-produce dipicolylamine-alendronate (DPA-alendronate), which has the radionuclide binding part separated from the BP by a spacer. After labeling the agent with (99m)Tc ([(99m)Tc]DPA-alendronate), the investigators compared its biodistribution and use as an imaging agent against [(99m)Tc]MDP in normal Balb/c mice (3). In another study the investigators compared the ex vivo biodistribution and imaging characteristics of (188)Re(CO)(3)-labeled DPA-alendronate ([(188)Re(CO)(3)]-alendronate) to those of clinically approved (188)Re-hydroxyethylidene-1,1-diphosphonate ([(188)Re]-HEDP) (6).ä |