Traitement adjuvant du cancer du sein localise a haut risque de rechute : et maintenant. les diphosphonates
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Gadolinium phosphonates as MR imaging contrast agents: physiologic effects in rabbit hearts.
The hemodynamic effects of the diphosphonate terminus of a new infarct-avid magnetic resonance (MR) imaging agent, gadolinium-DTPA (diethylenetriamine-pentaacetic acid) HPDP (1-hydroxo-3-aminopropane-1,1-diphosphonate), and HEDP (hydroxyethyl-1,1-diphosphonate) (a simple diphosphonate terminus model) have been evaluated at MR imaging doses in both isolated and intact rabbit hearts. Rapid injections of the sodium salt of the diphosphonates reversibly depressed left ventricular developed pressure and its first derivative (dP/dt) but did not affect the in vivo heart rate. Hemodynamic depression was prevented by the co-administration of two equivalents of calcium ion per diphosphonate terminus in the isolated heart and by either slow infusion or co-administration of one equivalent of calcium ion per diphosphonate terminus in the in vivo heart. Therefore, if these agents are to be used in MR imaging of acute myocardial infarction, appropriate measures should be taken to prevent negative inotropic effects.
Animals↗
Effects of a 120 day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasure.
The effects of immobilization on bone mass and bone remodeling in patients with spinal cord injuries are known to simulate weightlessness-induced bone changes in astronauts. Nevertheless, immobilization has never been investigated using histomorphometric studies in healthy volunteers. Twenty healthy male volunteers participated in a '120 day bed-rest' experiment in the USSR. Bone biopsy cores of iliac crest were taken before and at the end of the period of bed-rest. The subjects were divided into five groups. Five subjects underwent a normal ambulatory life (control subjects); three subjects were placed on continuous bed-rest for 120 days (complete immobilization); four subjects were immobilized and underwent a controlled training program; four subjects were immobilized and received treatment with potassium diphosphonate (ethane-1,hydroxy-1,diphosphonate 900 mg/day, per os); and four subjects were immobilized and received diphosphonate plus physical exercise. Parameters of bone mass and bone cellular activities (osteoblastic formation and osteoclastic resorption) were measured using automatic and semi-automatic image analysis systems. Bone mass remained constant in each group. Cellular activity measurements showed that in completely immobilized men, the mineralization rate was lower than in controls without change in osteoid parameters; in contrast, osteoclastic parameters were increased. In immobilized men given the training program, bone formation was normal and bone resorption was increased. In immobilized men treated with diphosphonate, osteoid parameters and resorption activity were decreased. In immobilized men with diphosphonate plus training, the osteoid parameters and the resorption activity were reduced but to a lesser degree than in immobilized men with diphosphonate alone. Failure of bone loss in normal immobilized subjects differed from results found in paraplegic patients. However, a decrease in mineralization rate and an increase in bone resorption activity were found in both studies. Exercise stimulated bone resorption and diphosphonate inhibited the osteoclastic activity. These data emphasize the difficulties in finding good models to stimulate spaceflight conditions on earth. Comparative studies must be done using bone biopsies to determine more precisely the effects of weightlessness on the human skeleton.
Adult↗
Influence of bivalent cations, phosphate and complexing substances on inorganic pyrophosphate in the microsomal fraction of isolated rat odontoblasts.
The influence of three diphosphonates, ethane-1-hydroxy 1.1. diphosphonate, methane-diphosphonate and dichloromethane diphosphonate, on inorganic pyrophosphatase (PPiase, E.C. 3.6.1.1.) was investigated. The inhibition by the diphosphonates appeared to be due to their complexation with a bivalent cation, probably Zn2+, which acts as a cofactor for the enzyme. The influence of calcium and inorganic phosphate (Pi) on the PPiase activity was studied in the presence and absence of several complexing substances, including the diphosphonates. Ca2+ alone inhibited the enzyme whereas, in the presence of EDTA, a Ca2+ stimulation of the PPiase was observed which was substrate-dependent and had an optimal activity at a Ca2+:PP4-i ratio of 1:1. There was a small inhibition of the PPiase activity by Pi which was not influenced by the substrate used.
Animals↗
99mTc-MDP accumulation mechanisms in bone.
The accumulation mechanisms of technetium-99m methylene diphosphonate were investigated using fetal mice calvaria, osteoblast-like cells, collagen sponges, and hydroxyapatite powder. Technetium-99m methylene diphosphonate accumulation was found consistently in the area of cells growing out from calvarial fragments cultured for 10 days. Accumulation was also seen on autoradiographs of calvarial fragments immediately fixed with 90% ethanol. The accumulated technetium-99m methylene diphosphonate in cultured calvarial fragments was removed by 100 mmol/L pyrophosphate and 378 mmol/L ethylenediaminetetraacetic acid, however, residual accumulations were still clearly visible. There was no relation between the osteoblast-like cell number and technetium-99m methylene diphosphonate accumulation. Technetium-99m methylene diphosphonate did not accumulate in collagen sponges. These findings suggest that the accumulation of technetium-99m methylene diphosphonate is by both chemical adsorption onto the surface of the hydroxyapatite in bone and incorporation into the crystalline structure of hydroxyapatite.
Adsorption↗
Selective uptake of 99mTc complexes and 67Ga in acutely infarcted myocardium.
The suitability of various radiopharmaceuticals (99mTc-tetracycline analogs, 99mTc-glucoheptonate, 99mTc-diphosphonate, and 67Ga-citrate) for use in imaging acute myocardial infarction was assessed by determining their biologic distributions in experimentally infarcted dogs. The highest infarct-to-normal myocardial concentration ratio was found with 99mTc-diphosphonate (27.9:1); the highest infarct-to-liver ratio was also found with 99mTc-diphosphonate (15.9:1). The infarct-to-bone ratio, however, was 0.4:1 with 99mTc-diphosphonate. There was an excellent positive linear correlation between blood-flow reduction and uptake of the radiopharmaceutical after a threshold reduction in blood flow with 99mTc-glucoheptonate and 99mTc-tetracycline. Technetium-99m-tetracycline accumulated only in infarcted tissue while 99mTc-diphosphonate was increased in both ischemic and infarcted tissue. Thus, 99mTc-diphosphonate has characteristics best suited for scintigraphic imaging. Since 99mTc-tetracycline accumulates only in infarcted tissue, however, this tracer more accurately defines the size of an acute infarction.
Animals↗
Quantitative bone scanning in the diagnosis of aluminium osteomalacia.
Skeletal uptake of diphosphonate was measured by emission tomography in 30 patients on chronic dialysis treatment. In 19 patients mean plasma aluminium concentrations, measured over the preceding 12 months, were 'high' (greater than 1.0 mumol/l, and in the other 11 were 'low' (less than 1.0 mumol/l). There was a strong correlation between serum alkaline phosphatase and skeletal uptake of diphosphonate in each group, but no difference in diphosphonate uptake between the groups. Additionally, when six patients with positive desferrioxamine tests were matched for serum alkaline phosphatase with six patients from the 'low' aluminium group there was no significant difference in uptake of diphosphonate (median and range 7.2; 5.2-16.5 and 5.9; 2.7-10.8 respectively). We conclude that skeletal uptake of diphosphonate is not suppressed in patients with moderate aluminium loading, but reflects bone turnover as indicated by serum alkaline phosphatase. Quantitative bone scintigraphy is not a useful discriminator for early aluminium osteomalacia.
Adult↗
Structural diversity of the oxovanadium organodiphosphonate system: a platform for the design of void channels.
The hydrothermal reactions of a vanadium source, an appropriate diphosphonate ligand, and water in the presence of HF provide a series of compounds with neutral V-P-O networks as the recurring structural motif. When the {O3P(CH2)(n)PO3}4- diphosphonate tether length n is 2-5, metal-oxide hybrids of type 1, [V2O2(H2O){O3P(CH2)(n)PO3}] x xH2O, are isolated. The type 1 oxides exhibit the prototypical three-dimensional (3-D) "pillared" layer architecture. When n is increased to 6-8, the two-dimensional (2-D) "pillared" slab structure of the type 2 oxides [V2O2(H2O)4{O3P(CH2)6PO3}] is encountered. Further lengthening of the spacer to n = 9 provides another 3-D structure, type 3, constructed from the condensation of pillared slabs to give V-P-O double layers as the network substructure. When organic cations are introduced to provide charge balance for anionic V-P-O networks, oxides of types 4-7 are observed. For spacer length n = 3, a range of organodiammonium cations are accommodated by the same 3-D "pillared" layer oxovanadium diphosphonate framework in the type 4 materials [H3N(CH2)(n)NH3][V4O4(OH)2 {O3P(CH)3PO3}2] x xH2O [n = 2, x = 6 (4a); n = 3, x = 3 (4b); n = 4, x = 2 (4c); n = 5, x = 1 (4d); n = 6, x = 0.5 (4e); n = 7, x = 0 (4f)] and [H3NR]y[V4O4(OH)2 {O3P(CH)3PO3}2] x xH2O [R = -CH2(NH3)CH2CH3, y = 1, x = 0 (4g); R = -CH3, n = 2, x = 3 (4h); R = -CH2CH3, y = 2, x = 1 (4i); R = -CH2CH2CH3, y = 2, x = 0 (4j); cation = [H2N(CH2CH3)2], y = 2, x = 0 (4k)]. These oxides exhibit two distinct interlamellar domains, one occupied by the cations and the second by water of crystallization. Furthermore, as the length of the cation increases, the organodiammonium component spills over into the hydrophilic domain to displace the water of crystallization. When the diphosphonate tether length is increased to n = 5, structure type 5, [H3N(CH2)2NH3][V4O4(OH)2(H2O){O3P(CH2)5PO3}2] x H2O, is obtained. This oxide possesses a 2-D "pillared" network or slab structure, similar in gross profile to that of type 2 oxides and with the cations occupying the interlamellar domain. In contrast, shortening the diphosphonate tether length to n = 2 results in the 3-D oxovanadium organophosphonate structure of the type 7 oxide [H3N(CH2)5NH3][V3O3{O3P(CH2)2PO3}2]. The ethylenediphosphonate ligand does not pillar V-P-O networks in this instance but rather chelates to a vanadium center in the construction of complex polyhedral connectivity of 7. Substitution of piperazinium cations for the simple alkyl chains of types 4, 5, and 7 provides the 2-D pillared layer structure of the type 6 oxides, [H2N(CH2CH2)NH2][V2O2{O3P(CH)(n)PO3H}2] [n = 2 (6a); n = 4 (6b); n = 6 (6c)]. The structural diversity of the system is reflected in the magnetic properties and thermal behavior of the oxides, which are also discussed.
Journal Article↗
Evolution of the structural chemistry of vanadium organodiphosphonate networks and frameworks: structural consequences of fluoride incorporation in the development of stable phases with void channels.
Hydrothermal reactions of solutions containing a vanadate source, an organodiphosphonate, an organonitrogen component, and HF (V/P/O/F) yield a series of oxyfluorovanadium-diphosphonates with charge-compensation provided by organoammonium cations or hydronium cations. While V/P/O/F networks provide the recurrent structural motif, the linkage between the layers and the details of the polyhedral connectivities within the layers are quite distinct for the five structures of this study. [H2pip][V4F4O2(H2O)2{O3P(CH2)3PO3}2] (1) (pip = piperazine) is a conventional three-dimensional (3D) "pillared" layer structure, whose V/P/O/F networks are buttressed by the propylene chains of the diphosphonate ligands. In contrast, [H2en][V2O2F2(H2O)2{O3P(CH2)4PO3}] (2) and [H2en]2[V6F12(H2O)2{O3P(CH2)5PO3}2 {HO3P(CH2)5PO3H}] (3) are two-dimensional (2D) slablike structures constructed of pairs of V/P/O/F networks sandwiching the pillaring organic tethers of the diphosphonate ligands. Despite the common overall topology, the layer substructures are quite different: isolated {VO5F} octahedra in 2 and chains of corner-sharing {VO(3)F(3)} octahedra in 3. The 3D structure of [H2en]2[V7O6F4(H2O)2{O3P(CH2)2PO3}4].7H2O (4.7H2O) exhibits a layer substructure that contains the ethylene bridges of the diphosphonate ligands and are linked through corner-sharing octahedral {VO6} sites. The connectivity requirements provide large channels that enclose readily removed water of crystallization. The structure of [H3O][V3F2(H2O)2{O3P(CH2)2PO3}2].3.5H2O (5.3.5H2O) is also 3D. Because of the similiarity with 4.7H2O, it exhibits V/P/O/F layers that include the organic tethers of the diphosphonates and are linked through corner-sharing {VO6} octahedra. In contrast to the network substructure of 4.7H2O, which contains binuclear and trinuclear vanadium clusters, the layers of 5.3.5 H2O are constructed from chains of corner-sharing {VO4F2} octahedra. Thermal studies of the open framework materials 4 and 5 reveal that incorporation of fluoride into the inorganic substructures provides robust scaffoldings that retain their crystallinity to 450 degrees C and above. In the case of 4, dehydration does not change the powder X-ray diffraction pattern of the material, which remains substantially unchanged to 450 degrees C. In the case of 5, there are two dehydration steps, that is, the higher temperature process associated with loss of coordinated water. This second dehydration results in structural changes as monitored by powder X-ray diffraction, but this new phase is retained to ca. 450 degrees C. The materials of this study exhibit a range of reduced oxidation states: 1 is mixed valence V(IV)/V(III) while 2 and 4.7H(2)O are exclusively V(IV) and 3 and 5.3.5H2O are exclusively V(III). These oxidation states are reflected in the magnetic properties of the materials. The paramagnetism of 1 arises from the presence of V(III) and V(IV) sites and conforms to the Curie-Weiss law with C = 2.38 em K/(Oe mol) and = -66 K with mu(eff) (300 K) = 4.33 mu(B). Compounds 3-5 exhibit Curie-Weiss law dependence of magnetism on temperature with mu(eff) (300 K) = 5.45 mu(B) for 3 (six V(III) sites), mu(eff) = 4.60 mu(B) for 4 (seven V(IV) sites) and mu(eff) = 4.13 mu(B) for 5 (two V(III) sites). Compound 2 exhibits antiferromagnetic interactions, and the magnetism may be described in terms of the Heisenberg linear antiferromagnetic chain model for V(IV). The effective magnetic moment at 300 K is 2.77 mu(B) (two V(IV) sites).
Journal Article↗
Relationship of inorganic pyrophosphatase and para-nitrophenylphosphatase activities of alkaline phosphatase in the microsomal fraction of isolated odontoblasts.
Some properties of inorganic pyrophosphatase (PPiase EC 3.6.1.1.) and para-nitrophenylphosphatase (p-NPPase EC 3.1.3.1) in the microsomal fraction of odontoblasts were investigated. The ratio of Mg2+:p-NPP and Mg2+:PPi for optimal enzyme activities was 1:1. A mutual substrate competition for PPiase and p-NPPase was described. In the presence of 0.1 mM EDTA, Mg2+ alone was not able to reactivate p-NPPase or PPiase. Instead, Zn2+ and Co2+ reactivated the PPiase, indicating they might act as cofactors for the enzyme. Mg2+ increased the PPiase activity, probably because Mg PP2-i was the true substrate for the enzyme. The diphosphonates ethane-1-hydroxy 1,1 diphosphonate (EHDP), methane diphosphonate (MDP) and dichloromethane diphosphonate (Cl2MDP) inhibited the PPiase activity.
4-Nitrophenylphosphatase↗
Biokinetics of bone tracers by means of deconvolution analysis--comparison of 99mTc MDP, 99mTc DPD and 99mTc EHDP.
Transfer functions of 99mTc methylene diphosphonate (MDP), 99mTc 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and 99mTc ethane-1-hydroxy-1,1-diphosphonate (EHDP) into bone and extravascular fluid of soft tissues were determined in 5 dogs by deconvolution analysis of the time-course of plasma, soft tissue and bone radioactivity. The transfer rates 5 min after injection--indicating the rapid exchange of the tracer between plasma and the extravascular fluid--decrease in the order MDP greater than EHDP greater than DPD (P less than 0.05). The transfer rates into bone--determined from transfer rates between 30 and 60 min--decreased in a different order, i.e. MDP greater than DPD greater than EHDP (P less than 0.05). The fractional bone uptake of diphosphonates estimated from the ratio of early to late transfer rates was slightly greater for DPD than for MDP and EHDP respectively. The difference between DPD and MDP was not significant (P greater than 0.05). The average bone and soft tissue concentrations of DPD 60 min after injection were greater than that of MDP and EHDP due to different plasma concentrations (DPD greater than EHDP greater than MDP), whereas the bone-to-soft tissue ratios decreased in the sequence MDP greater than DPD greater than EHDP (P less than 0.05).--Our results reveal different biokinetics of MDP, DPD and EHDP explaining variations in osseous and soft tissue uptake suggesting that deconvolution analysis could play an important role in bone scan interpretation.
Animals↗
Metabolic and hormonal factors influencing extrarenal buffering of an acute acid load.
This study evaluates metabolic and hormonal factors influencing extrarenal buffering of an acute acid load. Phosphate deprivation of 2 weeks duration was associated with enhanced extrarenal acid buffering. The enhanced extrarenal buffering capacity of phosphate deprivation was not dependent on the presence of parathyroid glands. Parathyroid hormone administration to phosphate-deprived rats promoted a further enhancement of the buffering capacity of an acid load. Blood pH and HCO3 during acid loading were not significantly different between control and diphosphonate-treated rats and between phosphate-deprived rats and phosphate-deprived rats treated with diphosphonate. The mortality rate, however, was significantly higher in diphosphonate-treated rats than in rats not receiving the drug suggesting that diphosphonate blunts the buffering of an acid load in both control and phosphate-deprived rats. Chronic vitamin D administration and acute administration of arginine vasopressin in pharmacologic doses were associated with significant enhancement of buffering capacity as compared to control rats. Thyrocalcitonin administration to intact but not thyroparathyroidectomized rats was associated with diminished capacity to buffer an acid load. These data demonstrate that the buffering of an acute acid load is influenced by a number of dietary and hormonal factors probably acting at the level of the bone.
Acid-Base Equilibrium↗
Extraskeletal localization of 99mTc-labeled bone-seeking tracers in bone scintigraphy.
In this article clinical examples of extraskeletal localization of technetium-99m (99mTc)-labeled diphosphonate are described. In several of these cases this finding was relevant for clinical decision-making. 99mTc-labeled diphosphonates have been used for skeletal imaging since 1971, and from 1973 on many reports of extraskeletal localizations of these agents have been published. This visualization can be due to (1) an abnormality of the excretory route of 99mTc-labeled diphosphonate or (2) increased uptake in pathologically altered tissues and organs. The latter has been recorded in a multitude of disease processes, such as ischaemic injury, inflammatory processes, benign or malignant neoplasms, non-skeletal metastases, malignant pleuritis, scars, radiation injury and amyloidosis. Although the precise mechanism of extraskeletal uptake of 99mTc-labeled diphosphonate remains uncertain, binding of this radiopharmaceutical to calcium-containing compounds is thought to play a critical role.
Adult↗
High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.
We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.
Bone Neoplasms↗
Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection.
Previous studies suggest that sequential technetium-99-hydroxymethyl diphosphonate bone scanning and indium-111 leukocyte scintigraphy may play a role during revision arthroplasty. Preoperative sequential imaging was compared with joint aspiration and clinical assessment during revision knee or hip arthroplasty. Scans were considered positive if indium-111 leukocyte uptake was incongruent or focally more intense than that of technetium-99-hydroxymethyl diphosphonate uptake. Of 166 cases, 22 were infected. Sequential technetium-99-hydroxymethyl diphosphonate and indium-111 leukocyte imaging was 64% sensitive and 78% specific. Fever, physical findings, or sedimentation rate did not identify infection reliably, and preoperative aspirate culture was only 28% sensitive. Positive scintigraphy increased the likelihood of finding infection intraoperatively from 14% to 30%, although negative scintigraphy decreased this likelihood to 7%. Based on the current study, the routine use of sequential technetium-99-hydroxymethyl diphosphonate and indium-111 leukocyte imaging cannot be advocated for differentiating occult infection from mechanical failure in painful, loose total joint arthroplasties.
Bacteriological Techniques↗
Effects of intravenous etidronate and oral corticosteroids in fibrodysplasia ossificans progressiva.
There is no known effective therapy for fibrodysplasia ossificans progressiva. Ethane-1-hydroxy-1-diphosphonate has been studied because of its inhibitory effect on bone mineralization and its potential to impair the rapid ossification process observed after acute episodes of fibrodysplasia ossificans progressiva. In an open study, the effects of intravenously administered ethane-1-hydroxy-1-diphosphonate and oral corticosteroids in the treatment of fibrodysplasia ossificans progressiva was evaluated. Thirty-one fibrodysplasia ossificans progressiva attacks were observed in seven patients during the mean followup of 6 years. In 29 attacks, the authors observed a rapid diminution of local inflammation, swelling, and pain during the first 7 days of treatment. However, despite the ethane-1-hydroxy-1-diphosphonate treatment, 10 new ossifications were observed, causing severe deterioration of joint mobility in all affected patients. In 21 attacks, no new ectopic ossification appeared. The radiologic pattern of preexisting ossifications did not change during the treatment. There are no data in the literature describing the percentage of acute episodes leading to an ossification. The results suggest the possibility that intravenous administration of ethane-1-hydroxy-1-diphosphonate and oral steroids may be helpful for the treatment of fibrodysplasia ossificans progressiva, but more control data on the spontaneous resolution of early flareups are needed.
Administration, Oral↗
The effects of various anti-calcific, anti-rheumatic and anti-inflammatory drugs on local (simple) calcergy induced by lead acetate in the mouse.
The diphosphonate compound ethane-hydroxy-1, 1-diphosphonate (EHDP) is an effective inhibitor of the calcification reaction induced by the subcutaneous injection of lead acetate in the mouse. Dichloromethylene diphosphonate (CL2MDP) has no such effect and prednisolone and sodium aurothiomalate are also ineffective in inhibiting the reaction. The rate of resorption of the calcified plaque is decreased by C12MDP when this is administered on an extended basis. This effect disappears after prolonged treatment so that EHDP, calcitonin and C12MDP have no effect after 7 weeks of daily treatment.
Animals↗
Anticancer-agent-linked phosphonates with antiosteolytic and antineoplastic properties: a promising perspective in the treatment of bone-related malignancies?
Bisphosphonates are compounds with a high affinity for bone and other calcified tissues. They inhibit tumor-induced bone destruction and the associated hypercalcemia by hindering the activity of the osteoclasts. Owing to a long biological half-life of bisphosphonates in the bone, a treatment using a prophylactic regimen seems possible. This paper summarizes preclinical studies with the bisphosphonate 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid and two methyl derivatives; 3-N,N-dimethylamino-1-hydroxypropylidene-1,1-diphosphonic acid and 4-N,N-dimetyhlamino-1-hydroxybutylidene-1,1-diphosphonic acid with respect to their bone-protecting activity in therapy as well as in prophylaxis. To find substances that are useful for the treatment of primary tumor, as well as bone metastasis, we synthesized and tested cis-diammine[nitrilotris(methylphosphonato)(2-)-O1,N1]platin um(II) and cis-diammine[( bis-(phosphonatomethyl)amino]acetato(2-)-O1,N1)platinum(II), which contain both an osteotropic and an antineoplastic moiety. Experiments were carried out: (a) in the intratibial transplanted Walker carcinosarcoma 256B of the rat, which mimics osteolytic bone metastasis, and (b) in the transplantable osteosarcoma of the rat, which shows a histology and metastatic pattern similar to that found in man. These investigations indicate that it is possible to effect adjuvant therapy of bone metastases by combination of two compounds with different properties into one structure without losing the therapeutic characteristics of the parent compounds. They thus provide evidence that it may be possible to design compounds well suited for the therapeutic or prophylactic treatment of bone-related malignancies.
Animals↗