Search results for "phosphonates"

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases.

2017

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are ofte…

V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…

2010

Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid

2016

Background Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68Ga-labelled analogues, endoradiotheraphy with 177Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Methods Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTAPAM and DOTAZOL(MM1.MZ) were successfully synthesized. The ligands were labe…

Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging

2019

Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans-cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111In-labelled Tz to image TC…

Wytwarzanie penicyliny G przez Penicillium chrysogenum jako marker biodegradacji związków fosfonoorganicznych

2011

Fragmentations and reactions of protonated O,O-dimethyl ethylphosphonate and some isotopomers produced by electrospray ionisation in an ion trap mass…

2008

Abstract The fragmentation behaviour of protonated O , O -dimethyl ethylphosphonate and its isotopomers deuterated in the α- and β-positions of the ethyl group and their fragment ions, particulary EtP(O)OMe + ( IV ), have been investigated both experimentally in an ion trap mass spectrometer and theoretically by electronic structure calculations at the B3LYP level. Of particular interest is the finding that the phosphonium ion IV eliminates ethene with hydrogen/deuterium loss from both the α-and β-positions. The initial step for both routes involves ethyl migration from P to O to form the ion MeOP + OEt which then loses ethene by two mechanisms, both of which lead to the same products. That…

Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells

2012

Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear. As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells tre…

Review and update on drugs related to the development of osteonecrosis of the jaw

2019

Conflict of interest Conclusions of the working group on “New drugs related to the de-velopment of osteonecrosis of the jaw”. Spanish Society of Cranio-mandibular Dysfunction and Orofacial Pain and Spanish Society of Oral Medicine SEDCYDO-SEMO joint International Meeting: 30th SEDCYDO annual meeting & 15th SEMO Congress. Bilbao (Spain); June, 2019. [EN] Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of cer-tain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or a…

Improving adherence in osteoporosis: a new management algorithm for the patient with osteoporosis

2011

Introduction: Bisphosphonates are the first-choice treatment for osteoporosis. They effectively increase bone mineral density, reduce markers of bone resorption, and lower the incidence of new fractures in patients with osteoporosis-related fracture. However, the efficacy observed in clinical trials may not be realized in a real-life setting, partly due to poor adherence to therapy, with a significant worsening of clinical outcomes. Several issues contribute to poor adherence to osteoporosis medication, including inconvenient dosing regimens and concerns about possible adverse events. Although strategies to improve adherence have been investigated, new approaches are required. Areas covered…

Radiodensitometric study for evaluation of bone mineral density around dental implants after zoledronic acid treatment in ovariectomized rats

2017

Background The purpose of this study was to evaluate the effects of intravenous zoledronic acid applied systemically on osseointegration of dental implants and the surrounding bone mineral density (BMD) in the ovariectomized rats. Material and Methods 36 rats were divided into three groups: control (CTRL), ovariectomy (OVX), and ovariectomy-zoledronic acid (OVX/ZOL). The rats in the CTRL group underwent sham surgery, while rats in OVX and OVX / ZOL group underwent ovariectomy. After 12 weeks, rats from OVX / ZOL were injected with 0.04 mg/kg ZOL intravenously once a week for 6 weeks. The rats from CTRL and OVX groups were injected with 0.9% NaCl. Implants were placed in the left tibia. Afte…