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(99m)Tc-Labeled trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid Panwar P; Chuttani K; Mishra P; Sharma R; Mondal A; Mishra AK; Chopra AMolecular Imaging and Contrast Agent Database (MICAD)-/-ä 2004[]; ä (ä): äCancers such as those of the breast, prostate, kidney, and thyroid have a high incidence of metastases, particularly in the bone, which results in bone resorption, pain, hypercalcemia, spinal compression, decreased mobility, and even fractures (1). In addition, osteoporosis (bone resorption), a common condition experienced most frequently by menopausal women as well as aging women and men, often leads to bone fractures in these individuals (2). Although chemo- and radiotherapy are often used to treat bone metastases, none of these treatments control the progression of this disease or result in a better prognosis for the patient. Because of their attraction to hydroxyapatite, a major component of bone, bisphosponates (BPs) or their nitrogen-containing derivatives (N-BPs) are the most commonly used compounds for the selective targeting and treatment of bone-related ailments observed during cancer metastases or osteoporosis (3, 4). The chemical structure, characteristics, and pharmacological behavior of BPs and their derivatives have been described by Hirabayashi and Fujisaki (3). Briefly, the parent BP compound contains a characteristic phosphate-carbon-phosphate (P-C-P) bond that is resistant to enzymatic digestion and has no substitution at the central carbon (5); N-BPs, however, have a nitrogen-containing moiety substituted on the carbon atom (6). BPs and N-BPs have been shown to inhibit bone-related events by different mechanisms (7), and N-BPs were reported to be 100- to 10,000-fold more potent than BPs (8). Both BPs and N-BPs are approved by the United States Food and Drug Administration for the treatment of bone diseases such as osteoporosis, Paget's disease of the bone, hypercalcemia, and bone metastases. In addition, these drugs are being evaluated in clinical trials for the treatment and imaging of different bone-related disorders. Accurate and early noninvasive detection of osteoporosis or bone metastases can assist in the development of a suitable treatment strategy and possibly improve the prognosis for a patient. Radiolabeled BPs, such as methyl diphosphonate (MDP) (9), hydroxymethylene diphosphonate, 1-hydroxyethylene diphosphonate, etc., are often used as imaging agents for the detection of bone remodeling (e.g., during cancer metastases) or repair (e.g., after a fracture) because these compounds tend to accumulate in osteoclasts at active bone sites (10). Although radiolabeled N-BPs have been used for the therapy of bone cancer in animals (11) and humans (12), no N-BPs have been evaluated or used for bone imaging. Panwar et al. (13) synthesized a (99m)Tc-labeled multidentated N-BP, trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid ((99m)Tc-CDTMP) and investigated its biodistribution in mice. The investigators also compared the whole-body scintigraphic images of rabbits treated with (99m)Tc-CDTMP with those obtained after treatment with (99m)Tc-MDP. In addition, imaging with (99m)Tc-CDTMP was performed on cancer patients with bone metastases, and the ratios of radioactivity accumulated in the bone lesion to soft tissue and the normal bone were determined.ä |
