Extraosseous uptake of metastatic lymph nodes of ureteral cancer on<sup>99</sup>Tc<sup>m</sup>hydroxymethylene diphosphonate bone scintigraphy

Kaida, Hayato; Ishibashi, Masatoshi; Baba, Kenichiro; Nishida, Hiroyuki; Matsuoka, Katsunari; Hayabuchi, Naohumi

doi:10.1259/bjr/14405146

Cited by 9 publications

(3 citation statements)

References 8 publications

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“…Interestingly, it was shown recently that treatment with zoledronate also significantly inhibited the growth of small cell lung cancer cells in the flanks of nude mice (35). The mechanism by which cancer cells accumulate Tc-99m hydroxymethylene diphosphonate is not understood, although tumor necrosis and calcification have been suggested to have a role in this process (20,21). Recent studies conducted in macrophages suggest the presence of an active, yet uncharacterized uptake mechanism, for which n-bisphosphonates and p-bisphosphonates compete (26).…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

Wakchoure

Merrell

Aldrich

et al. 2006

Clinical Cancer Research

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Purpose: Bisphosphonates (such as risedronate and zoledronate) are widely used inhibitors of bone resorption. Despite their in vitro antiproliferative effects in various cancer cells, bisphosphonates have not exhibited significant antitumor efficacy in animal models of visceral cancer, which may be due to their poor bioavailability. The diagnostic use of radioactive bisphosphonates has revealed the accumulation of bisphosphonates in mesothelioma, which prompted us to test the antitumor efficacy of bisphosphonates in this disease. Experimental Design and Results: Treatment with either risedronate or zoledronate (2 Â 10 À4 to 2 Â 10 À6 mol/L) inhibited the growth of AB12 and AC29 mouse mesothelioma cells and induced the accumulation of unprenylated Rap1A in these cells. Both these in vitro effects were reversed by geranygeraniol, an end product of the mevalonate pathway that these bisphosphonates inhibit. Both bisphosphonates also induced the phosphorylation of the p38 mitogen-activated protein kinase in AB12 and AC29 cells. The inhibition of p38 augmented bisphosphonate-induced growth inhibition in these cells. Bisphosphonate-induced p38 phosphorylation was not reversible by geranylgeraniol. Risedronate (15 mg/kg) and zoledronate (0.5 mg/kg) inhibited the growth of s.c. tumors and increased the median survival of mice with i.p. mesothelioma tumors in vivo. Discussion: In conclusion, risedronate and zoledronate inhibit the mevalonate pathway and induce p38 activation in mesothelioma cells in vitro. The effects on the mevalonate pathway dominate because the net result is growth inhibition. Both bisphosphonates also inhibit mesothelioma tumor growth in vivo and prolong the survival of mesothelioma-bearing mice. These results support further study of bisphosphonates in the management of mesothelioma.Mesothelioma, an asbestos-related neoplasm of the pleural and peritoneal space, occurs in f10,000 patients worldwide (1). Due to the long latency period for tumor development and the widespread use of asbestos for many years, the incidence is expected to rise until the year 2020 (2). The biological behavior is distinct from other solid tumors in that mesothelioma tends to grow in a sheet-like fashion, covering the surface of the pleura or peritoneum. It shows little tendency to invade, especially early in the course of the disease (3). Mesothelioma typically recurs even after the most aggressive attempts at surgical resection and is poorly responsive to radiotherapy and chemotherapy. Multimodality approaches have had a relatively small effect on the majority of the patients and have been associated with toxicity. The survival of patients with mesothelioma ranges between 4 and 12 months (4, 5). Clearly, new treatment modalities are needed.Bisphosphonates are synthetic analogues of the naturally occurring pyrophosphate. Depending on their molecular structure, these drugs can be divided into pyrophosphateresembling (p-bisphosphonates, such as clodronate) and nitrogen-containing bisphosphonates (n-bisphosphonates, su...

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Section: Discussionmentioning

confidence: 99%

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

Wakchoure

Merrell

Aldrich

et al. 2006

Clinical Cancer Research

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“…Various tumors at bone sites, whether primary or metastatic, are characterized by rapid bone deposition, and/or osteolytic lesions, and scans with 99m Tc-methylene diphosphonate (MDP) are very sensitive for visualization of tumor burden at osseous sites. 62 More importantly, the localization of 99m Tc-labeled BPs at extraskeletal sites could highlight pathological tissues, and recent experiences broaden the utility of 99m Tc-BP chelates to diagnose meningiomas, 63 cirrhosis of the liver, 64 cerebral infarction, 65 myocardial infarction, 66 osteosarcoma, 67 neurofibroma, 68 methotrexate osteopathy, 69 relapsing polychondritis, 70 and breast cancer. 71 As an example, 99m Tc-MDP detected calcifications in meningiomas arise from calvarial erosion, the formation of reactive bones, and tumor-induced calcification.…”

Section: Bisphosphonates In the Diagnosis Of Bone Diseasesmentioning

confidence: 99%

‘Magic bullets’ for bone diseases: progress in rational design of bone-seeking medicinal agents

2007

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An ideal therapeutic agent for bone diseases should act solely on bone tissue with no pharmacological activity at other anatomical sites. Current therapeutic agents, however, do not usually display a preferential affinity to bones and non-specifically distribute throughout the body after administration. Attempts to design bone-specific agents have relied on engineering a desired therapeutic agent with bone-seeking molecules so that the latter delivers the therapeutic agents specifically to bones. In this critical review, we summarize the latest attempts to engineer bone-seeking therapeutic agents based on formulating therapeutic agents with bisphosphonates, a class of compounds with high affinity to biological apatite. We first provide a relevant summary of the structure of bone mineral and bisphosphonates, highlighting the mode of interaction between these two entities. The use of bisphosphonates in the diagnosis of bone diseases is then presented, since this application helps us to understand the bone-carrier properties of bisphosphonates under physiological conditions. A summary of recent attempts to formulate bisphosphonates with traditional therapeutic agents to restrict their activities to bone tissues is then provided, with special emphasis on the structure-function relationships of the engineered compounds. Finally, attempts to use bisphosphonates to deliver macromolecular therapeutics (i.e., proteins) are summarized, based on recent data from the authors' lab. The collective research into bone-seeking medicinal agents is progressively laying the foundation for next-generation 'magic bullets' that display desirable activities at the disease sites with no undesirable activity on other organ systems. (164 references.).

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“…The Tc-99m MDP uptake in these lesions is due to ionic exchange at the crystalline surface 7. There are only few publications describing bone seeking radiotracer uptake in metastatic lymph nodes of primary tumours like ureteral cancer and osteosarcoma 8 9. The present case is unique as it describes Tc-99m MDP uptake in the metastatic lymph node from testicular tumour.…”

Section: Descriptionmentioning

confidence: 77%

Uptake of bone seeking radiotracer in the metastatic lymph node from testicular tumour

et al. 2022

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Extraosseous uptake of metastatic lymph nodes of ureteral cancer on⁹⁹Tc^mhydroxymethylene diphosphonate bone scintigraphy

Cited by 9 publications

References 8 publications

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

‘Magic bullets’ for bone diseases: progress in rational design of bone-seeking medicinal agents

Uptake of bone seeking radiotracer in the metastatic lymph node from testicular tumour

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Extraosseous uptake of metastatic lymph nodes of ureteral cancer on99Tcmhydroxymethylene diphosphonate bone scintigraphy

Cited by 9 publications

References 8 publications

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

Bisphosphonates Inhibit the Growth of Mesothelioma Cells In vitro and In vivo

‘Magic bullets’ for bone diseases: progress in rational design of bone-seeking medicinal agents

Uptake of bone seeking radiotracer in the metastatic lymph node from testicular tumour

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Extraosseous uptake of metastatic lymph nodes of ureteral cancer on⁹⁹Tc^mhydroxymethylene diphosphonate bone scintigraphy