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Biomedical subjects

M D Francis

Publications and source records attributed to M D Francis.

At least 37 records · Page 2Linked to original sources
PubMed1981

A comparison of skeletal uptakes of three diphosphonates by whole-body retention: concise communication.

Twenty normal volunteers had measurements of 24-hr whole-body retention (WBR) of three structurally related Tc-99m-labeled phosphonate skeletal imaging agents: (1-hydroxyethylidene) diphosphonate (HEDP), methylene diphosphonate (MDP), and hydroxymethylene diphosphonate (HMDP). The average WBR values, reflecting skeletal uptake, were 18.4, 30.3, and 36.6%, respectively. These results clearly illustrate that slight alterations in diphosphonate molecular structure have a significant effect upon specificity for osseous tissue, and thus may affect skeletal image quality and the usefulness of the WBR technique in diagnosing metabolic bone disease.

Adult↗
PubMed1980

Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. I. Synthesis and distribution in animals.

Technetium-99m hydroxymethylene diphosphonate (Tc-99M HMDP) is a new diphosphonate skeletal imaging agent. Animal studies show that Tc-99m HMDP has a higher uptake on bone and a more rapid clearance from the blood than any of the three technetium-labeled bone imaging agents in current use: Tc-99m methylene diphosphonate (DMP), Tc-99 (1-hydroxyethylidene) diphosphonate (HEDP), and Tc-99m pyrophosphate (PPi). On the basis of these animal studies, Tc-99m HMDP is a highly promising candidate for skeletal imaging.

Acute Disease↗
PubMed1980

Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. II. Comparison of Tc-99m hydroxymethylene diphosphonate (HMDP) with other technetium-labeled bone-imaging agents in a canine model.

Technetium-99m hydroxymethylene diphosphate (Tc-HMDP) was compared with the two other diphosphonates (Tc-MDP and Tc-HEDP) and Tc-99m pyrophosphate (Tc-PPi) in a canine model of acute myocardial infarction. The TC-HMDP showed higher uptake in infarcted myocardium than the other two diphosphonates, and uptake equivalent to that of Tc-PPi.

Animals↗
PubMed1980

Comparative evaluation of three diphosphonates: in vitro adsorption (C- 14 labeled) and in vivo osteogenic uptake (Tc-99m complexed).

We have investigated the in vitro adsorption of three C-14-labeled diphosphonates on calcium phosphate. The three are 1-hydroxy[1-14C]ethylidene diphosphonate (C-14 HEDP), [14C]methylenediphosphonate (C-14 MDP), and hydroxy[14C]methylenediphosphonate (C-14 HMDP). All three adsorbed significantly more, per mole of calcium, on amorphous calcium phosphate than on crystalline hydroxyapatite. Among the three diphosphonates, C-14 HMDP adsorbed--on both amorphous and crystalline calcium phosphate--to a greater degree than did the other two bone-seeking agents. Moreover, when HMDP was complexed with Sn(II) and Tc-99m, it produced a significantly higher uptake of Tc-99m, per mg of calcium, in an isolated in vivo site of osteogenesis. The mechanisms of adsorption are discussed relative to the hydroxyl group on the diphosphonate, to the solubility of the calcium salts to the diphosphonates, and to the form of the calcium phosphate. These studies form a working rationale for the clinically observed high contrast obtained with Tc-99m HMDP between normal bone and soft tissue, and between normal and abnormal bone.

Adsorption↗
PubMed1980

Preparation and biological distribution of technetium diphosphonate radiotracers synthesized without stannous ion.

Two HEDP complexes of technetium (either Tc-99 or a mixture of Tc-99 and Tc-99m) have been prepared without the use of stannous ion. The first, Tc(NaBH4)-HEDP, is synthesized by reduction of TcO4- with NaBH4 in the presence of excess HEDP; this is analogous to the preparation of Tc(Sn)-HEDP in commercial kits wherein SN(II) functions as the reductant. The second, Tc-HEDP, is prepared by substitution of HEDP onto the pre-formed, pre-reduced, technetium center TcBr62-. The HEDP-to-Tc ratio in Tc-HEDP was found to be 1.0 by double-labeling procedures (Tc-99 and [3H]HEDP), implying that in solution this material is polymeric or at least dimeric. Preparations of Tc(NaBH4)-HEDP and Tc-HEDP with Tc-99m are excellent bone-imaging agents in both rats and dogs. Tissue distribution studies in rats show that uptake of Tc(NaBH4)-HEDP and Tc-HEDP by the bone is at least equivalent to that achieved by Tc(Sn)-HEDP prepared in commercial kits with Sn(II) as the reductant. Tin is therefore not necessary for the bone-seeking properties of Tc(Sn)-HEDP, and the in vivo distribution of a given HEDP radiotracer seems to depend primarily on the presence of the HEDP ligand and not on the exact nature of the technetium complex itself. Synthesis of technetium radiotracers by a substitution route, rather than by redox, is practicable; this route has the potential of introducing hitherto unattainable flexibility and subtlety into the preparation of technetium radiotracers.

Etidronic Acid↗
PubMed1980

Gentisic acid: a new stabilizer for low tin skeletal imaging agents: concise communication.

In vitro stabilization of low-tin bone-imaging agents has previously been achieved with ascorbic acid. In this study gentisic acid is shown to be an equally effective antioxidant for the (1-hydroxyethylidene) diphosphonate (HEDP) and hydroxymethylenediphosphonate (HMDP) skeletal agents. In vitro studies show less than 2% free sodium [99mTc] pertechnetate at 24 hr with the gentisic acid stabilizer. Studies in guinea pigs at 3 and 24 hr--whether with C-14 or H-3-labeled gentisic acid as stabilizer--show no alteration in the biodistribution of either skeletal imaging agent by the addition of the gentisic acid. Gentisic acid is a safe and effective stabilizer, and clinical studies have shown bioequivalency with ascorbic acid.

Animals↗
PubMed1978

[32P] diphosphonate dose determination in patients with bone metastases from prostatic carcinoma.

In an initial safety study, phosphorus-32 (as diphosphonate) was administered intravenously to five patients with painful bone metastases from prostatic carcinoma; two patients received 9 mCi and three were given 3 mCi. Hematological, biochemical, ECG, x-ray, bone-scan data, and clinical observation, were followed for 2 mo. At both dose levels, bone-marrow depression was noted. One of the patients, who received 9 mCi, had only a slight dip in the levels of circulating white blood cells and platelets. The other 9-mCi patient was the only one with discrete metastases by bone scan; he had bone-marrow depression, from which he recovered, and was the only one of the five who had relief of bone pain.

Adenocarcinoma↗
PubMed1977

An in vitro and in vivo investigation of mellitate and ethane-1-hydroxy-1,1-diphosphonate in calcium phosphate systems.

Comparisons of mellitate (MA) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) have been carried out in studies of enamel etching, calcium phosphate crystal growth and animal calculus deposition. In enamel etch studies at pH 5, 6, or 7 and after treatment times of 5 or 170 min, EHDP was less damaging to enamel surfaces than MA as determined by scanning electron microscopy, grazing angle electron diffraction, and quantitative etch solution analyses. Both MA and EHDP inhibited hydroxyapatite crystal growth, although EHDP was more effective than MA. The formation of a tricalcium mellitate surface phase is suggested as the basis of the MA crystal growth effect on apatite. Both MA and EHDP also inhibited rat calculus formation, but EHDP was more effective than MA. The relation between crystal growth inhibition, surface phase solubility, and anti-calculus activity is discussed and a generalized principal for determining an effective inhibitor of calculus is suggested.

Animals↗
PubMed1977

Sites and mechanisms of localization of technetium-99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues.

This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus ((99m)Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for (99m)Tc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased (99m)Tc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between (99m)Tc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of (3)H-diphosphonate and (99m)Tc-P in infarcted myocardium. Autoradiographic studies with (3)H-diphosphonate revealed extensive labeling in the infarct periphery which contained necrotic muscle cells with features of severe calcium overloading, including widespread hypercontraction as well as more selective formation of mitochondrial calcific deposits. Autoradiography also demonstrated labeling of a small population of damaged border zone muscle cells which exhibited prominent accumulation of lipid droplets and focal, early mitochondrial calcification. Cell fractionation studies revealed major localization of both (99m)Tc-P and calcium in the soluble supernate and membrane-debris fractions of infarcted myocardium and less than 2% of total (99m)Tc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of (99m)Tc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum (99m)Tc-P activity retained the ability to adsorp to calcium hydroxyapatite and amorphous calcium phosphate. In vivo studies showed that concentration of human serum albumin (labeled with iodine-131) in infarcted myocardium reached a maximum of only 3.8 times normal after a circulation time of 96 h, whereas (99m)Tc-P uptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) (99m)Tc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of (99m)Tc-P results from selective adsorption of (99m)Tc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between (99m)Tc-P and tissue calcium levels mainly results from local differences in composition and physicochemical properties of tissue calcium stores and from local variations in levels of blood flow for delivery of (99m)Tc-P agents.

Animals↗
PubMed1976

Factors affecting uptake and retention of technetium-99m-diphosphonate and 99m-pertechnetate in osseous, connective and soft tissues.

The bone scanning complex, 99mTc-Sn-EHDP, consisting of the nuclide technetium-99m, stannous ion and ethane-1-hydroxy-1,1-diphosphonate, administered intravenously is retained in soft tissues in proportion to increasing calcium content of the tissues. Within bone tissue, the retention is proportional to vascularity and to surface area of calcium phosphate in bones and not necessarily to calcium and phosphate concentration. The nuclidic agent 99mTcO4-BUT NOT THE 99MTc-diphosphonate is selectively taken up by the thyroid and this uptake can be blocked by administering sodium perchlorate. Among the connective tissues studied, the tracheal cartilage seems to have the greatest potential to calcify with increasing age of the animal and man. Soft tissue does not retain the bone scanning complex 99mTc-Sn-EHDP but does retain 99mTcO4-.

Age Factors↗
PubMed1976

Bone scanning: radionuclidic reaction mechanisms.

One of the major successes of nuclear medicine in recent years has been the clinical utility of the 99mTc-labeled bone-imaging agents. This article is concerned with the evidence available for the mechanisms by which these and other such radiopharmaceuticals localize at sites in the skeleton.

Animals↗
PubMed1976

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Animals↗
PubMed1975

Distribution of 99mTc-Sn diphosphonate and free 99mTc-pertechnetate in selected soft and hard tissues.

Because increased uptake of 99mTc-diphosphonate (ethane-hydroxy-1, 1-diphosphonate) occasionally occurs in the anterior neck region, the possible increased affinity of the diphosphonate bone-scanning agent for cartilage was investigated. In vivo scintigraphic studies and organ analyses from rats and rabbits injected with this bone scintigraphic agent were performed. Trachea-to-muscle uptake ratios were a high 45:1 in adult Sprague-Dawley rats and approached the femur-to-muscle ratio of 93:1. Technetium-99m-diphosphonate uptake was also increased, but to a lesser extent, in xiphoid cartilage, tendon, and ear cartilage; this was proportional to the calcium content of the organ. The thyroid showed a high affinity for free pertechnetate but not 99mTc-diphosphonate, providing further evidence that the increased neck uptake of this 99mTc-diphosphonate is due to tracheal, not thyroid activity. In addition, premedication of three patients with 200 mg of potassium-perchlorate did not block this neck uptake. Interpretation of scintigraphs performed with 99mTc-diphosphonate that show lesions in the cervical spine should take into account the potential for false-positive readings caused by this increased tracheal uptake.

Achilles Tendon↗
PubMed1975

Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans.

A total of 1,355 patients from clinical trails with the 99mTc-labeled bone agent, Osteoscan (99mTc-Sn -EHDP), has shown a higher incidence of skeletal abnormalities than previously reported. Overall in this study, 60% of bone scans were abnormal in patients with nonosseous neoplasms. Carcinoma of breast, lung, and prostate yielded 67%, 64%, and 62% skeletal involvement, respectively. Over 50% of all the skeletal abnormalities for the neoplastic indications were detected in the thorax and vertebra while the skull, pelvis, and extremities accounted for 22%, 38%, and 34%, respectively.

Bone Neoplasms↗