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PubMed1985

A Walker 256 tumor-induced osteogenic small animal model for the evaluation of [99mTc] diphosphonate radiopharmaceuticals.

A mammalian model has been developed for the in vivo evaluation of bone imaging agents. The model is based upon the quantification of a discrete, initial secondary periosteal osteogenesis induced in cortical bone immediately adjacent to an intramuscularly implanted Walker 256 tumor in Fisher 344 rats. Evaluation of the model consists of a histopathological examination of the periosteal bone formation, biodistribution studies on 99mTc-MDP and 99mTc-HMDP commercial kit preparations, and biodistribution studies on two 99mTc-HEDP component fractions isolated after anion exchange chromatographic separations from an investigative "carrier added" preparation. Reversed phase HPLC separations of the 99mTc-MDP and 99mTc-HMDP commercial kit preparations illustrate distinct differences in chemical composition between the two bone agents.

Animals↗
PubMed1990

Fast (4-h) or slow (24-h) infusions of pamidronate disodium (aminohydroxypropylidene diphosphonate (APD)) as single shot treatment of hypercalcaemia.

Twenty-five patients with hypercalcaemia (ionised calcium, 1.57 +/- 0.04 mM; total calcium, 3.33 +/- 0.06 mM) due to malignancy were randomised to receive pamidronate (1 mg/kg body wt.) by infusion over 4 h (12 patients) or 24 h (13 patients). Forced saline diuresis was not utilised. Two patients died within 24 h and were not included in the analysis. Both groups combined (n = 23) showed a decrease in ionised calcium to 1.44 +/- 0.04 mM by 2 days (P less than 0.05 vs. day 0). By 4 days there had been a further fall to 1.27 +/- 0.05 mM (P less than 0.05 vs. day 2) and 7 days after treatment ionised calcium was 1.19 +/- 0.05 mM (P less than 0.05 vs. day 4). Total calcium declined from 3.33 +/- 0.06 to 2.65 +/- 0.11 mM over 7 days (P less than 0.001). Separate analyses of the two groups showed that the fast (4-h) infusion led to an earlier reduction in calcium than did the 24-h infusion (P less than 0.02), although after 7 days there was little difference between the two groups (4 h, 1.18 +/- 0.09 mM; 24 h, 1.23 +/- 0.06 mM, n.s.). Hypercalcaemic symptoms (analogue rating scale) improved between each of the time intervals 0, 4 and 7 days (P less than 0.05) and did not differ between the two groups. We recommend a single 4-h infusion of pamidronate (1 mg/kg) as primary treatment for malignancy-induced hypercalcaemia.

Calcium↗
PubMed1986

Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases--III. Considerations of interaction, binding and absorbed dose.

General considerations about the possible mechanisms of action of rather low dose ionizing radiation with bone metastases and stimulated nerve fibers reveal that only minute amounts of chemicals are produced by direct interaction of energetic electrons. Thus changes of the chemical milieu due to direct interaction must be ruled out in favour of a radiation-induced trigger reaction which may then initiate a cascade of cellular responses. Organ distribution studies of a series of radioiodinated benzylidenediphosphonates with H-, HO- and H2N- in the alpha- and p-position revealed best results for pHO-NH2 (BDP3). The microscopic distribution of 131I-DBP3 in bone tissue was monitored by autoradiography. Elevated uptake in normal (tibia) and neoplastic bone (experimental osteosarcoma) corresponded with the degree of vascularization and formation of new hydroxylapatite. Unlike the uptake in human osteoblastic bone metastases the experimental osteosarcoma of SD-rats accumulated 131I-BDP3 less than normal bone. This was due to the short volume doubling time, the delay of hydroxyl-apatite deposition and the formation of necroses. Theoretical replacement of 131I in iodinated BDP3 with radioisotopes emitting higher energy electrons yielded best bone metastasis/organ ratios for 32P labeled BDP3. The bone metastasis/bone marrow dose ratio by comparison with 131I labeled BDP3 is, however, almost equal. The isotopes 130I and 133I are not suited to the achievement of higher tumor/background doses although they are higher energy beta- -emitters than 131I. Because of their short physical half life and absence of different kinetics in normal and neoplastic bone no dose enhancement in bone metastases can be attained.

Animals↗
PubMed1989

Technetium-99m complexes of dimethylaminomethylene diphosphonate (DMAD)--I. Anion exchange HPLC characterization of 99mTc(NaBH4)-DMAD mixtures.

Radiopharmaceutical analogs prepared by sodium borohydride reduction of 99mTcO4- in the presence of DMAD have been characterized by anion exchange HPLC (high performance liquid chromatography) separation of the resulting mixture into component 99mTc-DMAD complexes. The distribution of complexes within a radiopharmaceutical formulation can be manipulated by controlling technetium concentration, pH, presence or absence of air, and time post reaction.

Borohydrides↗
PubMed1989

Technetium-99m complexes of dimethylaminomethylene diphosphonate (DMAD)--II. Biological distributions of 99mTc-DMAD components isolated by anion exchange HPLC.

HPLC isolated components of 99mTc(NaBH4)-DMAD mixtures exhibit significantly different biological properties than do analogous components of 99mTc(NaBH4)-MDP and 99mTc(NaBH4)-HEDP mixtures. Most importantly, 99mTc-DMAD components desorb from normal bone whereas analogous 99mTc-MDP and 99mTc-HEDP components do not. However, within an osteogenic rat model, an HPLC isolated 99mTc-DMAD component does not exhibit an unusually high abnormal/normal tibia uptake ratio.

Animals↗
PubMed2005

[What is the place of diphosphonates in the treatment of complex regional pain syndrome I?].

OBJECTIVES: To evaluate the efficacy of biphosphonates (BPs) in complex regional pain syndrome I or reflex sympathetic dystrophy and to specify their place in this chronic painful syndrome. METHODS: A literature review of Medline and Embase with use of a combination of 3 key words: biphosphonates therapy, reflex sympathetic dystrophy, complex regional pain syndrome I, controlled study. Each article was classified by 2 independent reviewers according to Aguilar's method into high, middle or low quality. RESULTS: Three second-generation BPs were tested in the treatment of reflex sympathetic dystrophy: pamidronate, alendronate and clodronate. Many open studies investigated pamidronate, but only 2 were randomised and controlled: a low-quality trial comparing pamidronate with placebo and a middle-quality trial comparing pamidronate with calcitonine. Two high-quality trials were performed, 1 with alendronate and 1 with clodronate. Middle-quality trial and high-quality trials reported positive effects on pain with BPs in recent reflex sympathetic dystrophy (disease duration less than eight months). Side effects (fever, asymptomatic hypocalcemia) were observed frequently but disappeared quickly. CONCLUSION: BPs can be used in recent reflex sympathetic dystrophy when calcitonin is inefficient or when calcitonin injections are not well tolerated.

Complex Regional Pain Syndromes↗
PubMed2006

ESI-FTICR mass spectrometric study of alcohol complexation properties of mono- and diphosphonate-bridged cavitands.

Alcohol complexation properties of eight mono- and diphenyl phosphonate-bridged cavitands were studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR) and theoretical calculations. The cavitands varied in number and position of phenyl phosphonate bridges and their orientation with respect to the cavity, length of the lower rim alkyl chains, and substituents at apical positions of the resorcarene skeleton. The specificities of the different cavitands toward primary, secondary, and tertiary alcohols varying long of the alkyl chain were investigated, together with the stabilities of the formed complexes. The number, position, and orientation of the P = O moieties affected the complex formation of the cavitands and stability of the complexes dramatically. Methyl groups at apical positions of the resorcarene skeleton also affected the complexation properties. Although length and branching of the alkyl chain of the alcohol influenced the complex formation, the effect on stability of the complexes was negligible.

Acetonitriles↗