pyrophosphate and Neoplasm-Metastasis

The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents.

Topics: Adult; Aged; Animals; Bone Neoplasms; Breast Neoplasms; Carcinoma, Squamous Cell; Colonic Neoplasms; Diphosphates; Female; Fluorine; Hodgkin Disease; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Rabbits; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient.

Topics: Adult; Age Factors; Aged; Bone and Bones; Bone Neoplasms; Computers; Diphosphates; Diphosphonates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Humans; Male; Neoplasm Metastasis; Organophosphonates; Phosphates; Radiation Dosage; Radionuclide Imaging; Technetium; Whole-Body Counting

An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore, immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1 breast tumor but also significantly preventing metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results in the eradication of light-irradiated primary tumors and the complete inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T cell response. These findings indicate that nanoparticle-mediated PDT can potentiate the systemic efficacy of checkpoint blockade immunotherapies by activating the innate and adaptive immune systems in tumor microenvironment.

Topics: Animals; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Chlorophyll; Combined Modality Therapy; Diphosphates; Humans; Immunotherapy; Light; Lipids; Lung Neoplasms; Mice; Nanoparticles; Necrosis; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Zinc

We aimed to test the ability of texture analysis to differentiate the spatial heterogeneity of (125)I-A5B7 anti-carcinoembryonic antigen antibody distribution by nano-single photon emission computed tomography (SPECT) in well-differentiated (SW1222) and poorly differentiated (LS174T) hepatic metastatic colorectal cancer models before and after combretastatin A1 di-phosphate anti-vascular therapy.. Nano-SPECT imaging was performed following tail vein injection of 20 MBq (125)I-A5B7 in control CD1 nude mice (LS174T, n=3 and SW1222, n=4), and CA1P-treated mice (LS174T, n=3; SW1222, n=4) with liver metastases. Grey-level co-occurrence matrix textural features (uniformity, homogeneity, entropy and contrast) were calculated in up to three liver metastases in 14 mice from control and treatment groups.. Before treatment, the LS174T metastases (n=7) were more heterogeneous than SW1222 metastases (n=12) (uniformity, P=0.028; homogeneity, P=0.01; contrast, P=0.045). Following CA1P, LS174T metastases (n=8) showed less heterogeneity than untreated LS174T controls (uniformity, P=0.021; entropy, P=0.006). Combretastatin A1 di-phosphate-treated SW1222 metastases (n=11) showed no difference in texture features compared with controls (all P>0.05).. Supporting the potential for novel imaging biomarkers, texture analysis of (125)I-A5B7 SPECT shows differences in spatial heterogeneity of antibody distribution between well-differentiated (SW1222) and poorly differentiated (LS174T) liver metastases before treatment. Following anti-vascular treatment, LS174T metastases, but not SW1222 metastases, were less heterogeneous.

Topics: Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal; Carcinoembryonic Antigen; Cell Line, Tumor; Colorectal Neoplasms; Diphosphates; Female; Heterografts; Humans; Iodine Radioisotopes; Liver Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Phenotype; Radiopharmaceuticals; Stilbenes; Tomography, Emission-Computed, Single-Photon

Purinergic signaling cascade includes the release of endogenous ATP and other agonists by chemical and mechanical stimuli, modulation of diverse cellular functions and subsequent ectoenzymatic inactivation. Basal release of extracellular purines and its physiological relevance remain controversial. Here we employed a combination of enzyme-coupled approaches for simultaneous bioluminescent (ATP, ADP, PP(i)) and fluorometric (AMP), adenosine, inosine, hypoxanthine) measurements of ATP and its metabolites without additional manipulations or derivatization of sampled biological fluids. By using these sensing techniques, extracellular purines were determined in various cells and tissues both at resting and pro-inflammatory conditions. The results obtained revealed the ability of endothelial, lymphoid and tumor cells to maintain extracellular ATP, ADP and adenosine at certain characteristic nanomolar levels. By quantifying the amounts of endogenously released and/or exogenously applied purines and their metabolites, these sensing techniques may be applied for evaluating purine-converting pathways on the cell surfaces and also for ex vivo analysis of purine homeostasis in the intact tissues. Furthermore, we provide novel insight into the mechanisms underlying tumorigenic effects of ATP by demonstrating the ability of metastatic prostate carcinoma PC3 and breast cancer MDA-MB-231 cells to maintain PP(i), which derives from extracellular ATP in the course of nucleotide pyrophosphatase/phosphodiesterase reaction. Collectively, the results imply a complex pattern of nucleotide turnover where extracellular ATP, ADP and adenosine are maintained at steady-state levels via conunterbalanced release and inactivation of ATP and other purines, and further suggest the importance of basal agonist release for continuous activation and/or desensitization of purinergic receptors.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Cell Line, Tumor; Chromatography, Thin Layer; Diphosphates; Enzyme Assays; Extracellular Fluid; Fluorometry; Homeostasis; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Inosine; Luminescent Measurements; Lymphocytes; Neoplasm Metastasis; Nucleosides; Nucleotides; Pyrophosphatases

Medulloblastoma (MB) is the most common malignant brain tumor in children and occurs mainly in the cerebellum. Important intracellular signaling molecules, such those present in the Sonic Hedgehog and Wnt pathways, are involved in its development and can also be employed to determine tumor grade and prognosis. Ectonucleotidases, particularly ecto-5'NT/CD73, are important enzymes in the malignant process of different tumor types regulating extracellular ATP and adenosine levels. Here, we investigated the activity of ectonucleotidases in three malignant human cell lines: Daoy and ONS76, being representative of primary MB, and the D283 cell line, derived from a metastatic MB. All cell lines secreted ATP into the extracellular medium while hydrolyze poorly this nucleotide, which is in agreement with the low expression and activity of pyrophosphate/phosphodiesterase, NTPDases and alkaline phosphatase. The analysis of AMP hydrolysis showed that Daoy and ONS76 completely hydrolyzed AMP, with parallel adenosine production (Daoy) and inosine accumulation (ONS76). On the other hand, D283 cell line did not hydrolyze AMP. Moreover, primary MB tumor cells, Daoy and ONS76 express the ecto-5'NT/CD73 while D283 representative of a metastatic tumor, revealed poor expression of this enzyme, while the ecto-adenosine deaminase showed higher expression in D283 compared to Daoy and ONS76 cells. Nuclear beta-catenin has been suggested as a marker for MB prognosis. Further it can promotes expression of ecto-5'NT/CD73 and suppression of adenosine deaminase. It was observed that Daoy and ONS76 showed greater nuclear beta-catenin immunoreactivity than D283, which presented mainly cytoplasmic immunoreactivity. In summary, the absence of ecto-5'NT/CD73 in the D283 cell line, a metastatic MB phenotype, suggests that high expression levels of this ectonucleotidase could be correlated with a poor prognosis in patients with MB.

Topics: 5'-Nucleotidase; Adenosine; Adenosine Deaminase; Adenosine Monophosphate; Adenosine Triphosphate; Alkaline Phosphatase; beta Catenin; Biomarkers, Tumor; Brain Neoplasms; Cell Line, Tumor; Cerebellum; Child; Diphosphates; Gene Expression Regulation, Neoplastic; Humans; Medulloblastoma; Neoplasm Metastasis; Organ Specificity; Phosphoric Diester Hydrolases; Prognosis; Pyrophosphatases; Signal Transduction

The value of radioisotope bone scanning at the time of presentation and serially during follow-up has been evaluated in 55 patients with biopsy-proven osteogenic sarcoma. Many of the patients studied were treated with adjuvant chemotherapy. Bone metastases were detected at presentation in only one patient and in a second patient, proximal extension of the primary tumor not evident on radiographs was demonstrated by the radioisotope technique. During fellow-up, 20 patients experienced bone metastases and each had an abnormal bone scan. Eleven of these patients were asymptomatic for bone metastases at the time the scan became abnormal. Seven patients experienced bone metastases as their first site of tumor recurrence. The detection rate for soft tissue metastases was low, but the scan indicated stump recurrence in three patients. Although the yield is small, bone scanning is justified at presentation be cause the results may profoundly after the management. During follow-up, routine bone cans are indicated in all patients, whether they have symptoms or not.

Topics: Adolescent; Adult; Bone Neoplasms; Child; Diphosphates; Diphosphonates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Prognosis; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup.

Topics: Bone Neoplasms; Child; Child, Preschool; Diphosphates; False Negative Reactions; Female; Humans; Infant; Male; Neoplasm Metastasis; Neuroblastoma; Radionuclide Imaging; Technetium

Thirty patients had bone scintigraphy with both Tc-99m pyrophosphate (Tc-PPi) and Tc-99m diphosphonate (Tc-HEDP). The images were given a composite rating for quality and the basis of three sets of criteria, and were also compared for the number of lesions detected by each agent. The two agents provided no difference in scan quality. Nevertheless, in ten of the 30 patients, at least two of the three readers detected with Tc-HEDP lesions that were not seen with Tc-PPi, and in two such cases all three readers considered the Tc-PPi scan normal. In another of these ten, two of three readers felt the Tc-PPi image was norm, whereas all three detected the lesion with Tc-HEDP. The reverse never occurred (P less than 0.01).

Topics: Bone Neoplasms; Diphosphates; Etidronic Acid; Evaluation Studies as Topic; Humans; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Abdomen; Adult; Diphosphates; Humans; Male; Neoplasm Metastasis; Osteosarcoma; Radionuclide Imaging; Technetium; Thorax

Topics: Adolescent; Adult; Aged; Bone and Bones; Bone Diseases; Bone Neoplasms; Child; Child, Preschool; Diphosphates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Adenocarcinoma; Adenocarcinoma, Scirrhous; Adult; Bone Neoplasms; Breast Neoplasms; Carcinoma; Diphosphates; Female; Humans; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Child; Child, Preschool; Diagnosis, Computer-Assisted; Diphosphates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Technetium

Metastatic soft tissue calcification is known to occur in hypercalcemia and is usually present in the kidneys, stomach and lungs. 1--3 This case presents two unusual features: 1) ectopic parathormone production in association with poorly differentiated lymphocytic lymphoma; and and 2) uptake of 99mTc-pyrophosphate in the liver in the absence of demonstrable abnormality at autopsy. The more usual sites of metastatic calcification also showed uptake of the radionuclide. We will discuss metastatic soft tissue calcification, ectopic parathyroid hormone production, hypercalcemia in malignancy and bone scan agent localization in soft tissues.

Topics: Aged; Bone Neoplasms; Calcinosis; Diphosphates; Female; Hormones, Ectopic; Humans; Hypercalcemia; Liver; Lymphoma, Non-Hodgkin; Neoplasm Metastasis; Parathyroid Hormone; Radionuclide Imaging; Technetium

Topics: Animals; Bone and Bones; Bone Neoplasms; Diphosphates; Diphosphonates; Female; Guinea Pigs; Humans; Isotope Labeling; Male; Neoplasm Metastasis; Phosphates; Quality Control; Radionuclide Imaging; Rats; Technetium

Three hundred and ten bone scintigraphies were carried out in patients with a carcinoma of the breast. The results of these studies were compared not only with radiological findings but also the clinical and paraclinical course of the patients, the period of observation being between 8 and 44 months. Amongst the scintigrams in which no abnormality was detected, approximately 3.3% were obtained in patients with osteolytic metastases, the majority of these patients also having a rapidly growing primary tumourmamongst the patients with zones of hyperfixation and, at the same time, non-fixing metastases, 14/22 diedvery rapidly with diffuse bone metastases, this confirming the notion of poor prognosis in this "false negative" group. 11.3% of the abnormal results involved patients who showed no bone lesions more than 6 months after radio-isotopic examination "false positives". Of these, 12/18 were single lessions (41%). 14% of examinations carried out on a routine basis demonstrated metastases for which clinical and/or radiological confirmation was obtained only 2 to 9 months later.

Topics: Bone Neoplasms; Breast Neoplasms; Diphosphates; Humans; Neoplasm Metastasis; Prognosis; Radionuclide Imaging; Technetium

Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis.

Topics: Bone Neoplasms; Carcinoid Tumor; Diphosphates; Female; Femoral Neoplasms; Frontal Bone; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Ovarian Neoplasms; Radionuclide Imaging; Rectal Neoplasms; Ribs; Spinal Neoplasms; Technetium

Lower neck uptake, frequently seen on anterior views of bone scans done with 99mTc-phosphate compounds, was studied in 122 patients to determine its incidence and etiology. Increased uptake was identified in the lower neck anteriorly in 46 patients (38%). In 14 of these, moderately severe to severe arthritis appeared to cause the uptake; metastatic disease was the cause in 8 cases; and in 1 case there was prominent uptake in the thyroid cartilage. Positioning artifact accounted for the uptake in the other 23 cases. Thyroid uptake was never observed.

Topics: Adult; Cervical Vertebrae; Diphosphates; Etidronic Acid; Humans; Laryngeal Cartilages; Neoplasm Metastasis; Osteoarthritis; Radionuclide Imaging; Spinal Diseases; Spinal Neoplasms; Technetium

Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Bone Diseases; Bone Neoplasms; Colonic Neoplasms; Diphosphates; Diphosphonates; Extremities; Femur; Gout; Hemangiosarcoma; Humans; Hypertrophy; Lumbar Vertebrae; Melanoma; Middle Aged; Neoplasm Metastasis; Osteoarthritis; Radionuclide Imaging; Spinal Neoplasms; Spinal Osteophytosis; Spondylolisthesis; Technetium

We have compared bone images from a number of patients using three instruments. In 38 patients, Cleon body images were compared with whole-body rectilinear scans. Cleon images were also compared with scintillation camera images of the trunk or extremities of 31 patients and of the skull of 70 patients. The Cleon was superior to the rectilinear scanner in resolution, lesion detectability, and speed of scanning. The Cleon and gamma camera were comparable in lesion detection, but the Cleon was consdierably faster. Clinical studies and comparative evaluation are presented.

Topics: Bone Neoplasms; Diphosphates; Evaluation Studies as Topic; Female; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Ribs; Skull Neoplasms; Technetium

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Diphosphonates; Female; Humans; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Reagent Kits, Diagnostic; Technetium

A positive 99mTc-pyrophosphate bone scan is reported in a proven case of large compact bone island. Pyrophosphate uptake in this case is presumed to be due to either large size or growth of the bone island. A radionuclide bone scan does not always differentiate bone islands from metastatic or inflammatory sclerotic bone lesions.

Topics: Adult; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Humans; Male; Melanoma; Neoplasm Metastasis; Radionuclide Imaging; Technetium

A comparative study on 99m-Tc-phosphate compounds (TcPP) in detecting tumor metastasis to bone and problems accompanying it are reported. TcPP revealed metastatic foci which are unrecognized by conventional bone survey. To recognize these foci, exclusion of following problems is necessary: Accumulation at front of neck, asymmetrical image of joint, increased bone density of the aged, Tc-photon absorption and radiotherapy effect. The mechanism of TcPP accumulation is discussed.

Topics: Absorption; Adult; Age Factors; Aged; Bone Neoplasms; Diphosphates; Elementary Particles; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Organophosphonates; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Bone scan findings (using 99mTc-stannous pyrophosphate) in five patients with diffuse metastatic carcinoma of the axial skeleton are reviewed. Although there were few visually recognizable asymmetries of tracer localization, the diffuse involvement was diagnosed through abnormally elevated counting rates in the axial skeleton, decreased visualization of the kidneys, and faint or absent visualization of the appendicular skeleton.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Carcinoma, Transitional Cell; Diphosphates; Humans; Kidney Neoplasms; Kidney Pelvis; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Ribs; Skull Neoplasms; Spinal Neoplasms; Sternum; Technetium

Technetium-99m labelled imidodiphosphate was prepared in the presence of stannous ions. It was evaluated as a bone-scanning agent in animals and patients. Comparative tissue distribution studies in mice showed a relatively higher uptake of radioactivity in bone when 99Tcm -labelled pyrophosphate and diphosphonate. Accumulation of radioactivity in soft tissues, especially kidneys, was less with this radiopharmaceutical. Results in patients were most satisfactory in delineating skeletal bone and identifying bone lesions with relatively small tracer doses of the radiopharmaceutical.

Topics: Animals; Bone and Bones; Bone Neoplasms; Diphosphates; Dogs; Female; Humans; Imides; Male; Mice; Middle Aged; Neoplasm Metastasis; Organophosphonates; Phosphates; Rabbits; Radionuclide Imaging; Technetium

Topics: Diphosphates; Dysgerminoma; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Technetium

The purpose of the present work is to "quantify" bone scanning, in order to calculate indices of localized uptake that will make it possible to differentiate between normal and pathological uptake, and approach an etiologicial diagnosis. The authors use an Elscint dual head whole body scanner and an offline video display calculator. The patient is given 8 mc technetium 99m pyrophosphate 4 hours prior to scanning. The whole body count is expressed in thousands of counts multipled by two so that the knee to whole body ratio is close to one, to facilitate comparison of the indices. Results show that the presence of metastases is demonstrated more clearly by using a ratio bone segment to whole body. Quantitative scanning with 99mTc-pyrophosphate makes it possible to: 1) detect bone metastases easily, 2) follow the metastases during treatment, 3) avoid the gross errors that can be made in nomquantitative scanning.

Topics: Bone Neoplasms; Diphosphates; Female; Humans; Knee; Male; Neoplasm Metastasis; Radionuclide Imaging; Spinal Neoplasms; Technetium

99MTc pyrophosphate has restored bone scintigraphy to the position of respectability it had lost with radiostrontium 85 and 87m, and it has rapidly become the method of choice for the detection of osteogenic hyperactivity. In cases of tumor the histologic disorder is frequently detected prior to the morphologic changes seen in X-ray pictures. The biophysical properties of 99mTc pyrophosphate provide high quality imaging of the skeleton. The scans or scintiphotos render possible a more sensitive and earlier diagnosis than radiography, though bone scanning does not of course supersede radiography. The two methods are complementary. In present day oncologic practice, however, bone scintigraphy with 99mTc pyrophosphate replaces to advantage the conventional radiographic "bone survey". In neurology the change is already appreciable and has proved its worth. In the light of results in 78 neurologic patients attention is drawn to the significant changes bone scintigraphy has brought about in diagnosis and therapeutic planning. The indications which have already emerged from this new method of nuclear neurology are tabulated, discussed and illustrated.

Topics: Adult; Aged; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Female; Fractures, Bone; Histiocytoma, Benign Fibrous; Humans; Male; Neoplasm Metastasis; Nervous System Diseases; Radionuclide Imaging; Skull Neoplasms; Technetium

The authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear.

Topics: Bone Diseases; Bone Neoplasms; Diphosphates; Epiphyses, Slipped; Humans; Joint Diseases; Knee Joint; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteoporosis; Radiography; Radionuclide Imaging; Spinal Diseases; Spondylitis; Spondylitis, Ankylosing; Technetium

A total of 146 patients were investigated for the presence of osseous metastases with 99mTc polyphosphate or 99mTc pyrophosphate bone scans. Results of bone imaging were retrospectively compared to roentgenographic results surveying similar anatomic areas in 128 patients. This comparison revealed that roentgenographic interpretations were in error in 19% of the cases. Thirty-three patients had bone scans and roentgenograms that were in agreement and considered abnormal, but in more than one third of these cases the patients had multiple abnormalities that were shown by the bone scan but were not recognized roentgenographically. In consideration of the low toxicity, ready availability, economy, shortened procedure time, and low radiation dose associated with the use of these new bone-seeking agents, it is concluded that they are superior to roentgenograms and previously utilized radionuclides for early detection of osseous metastases.

Topics: Bone Neoplasms; Carcinoma; Diphosphates; Fluorine; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging; Scintillation Counting; Strontium Radioisotopes; Urinary Bladder Neoplasms

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Diphosphates; Female; Fluorine; Humans; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Radioisotopes; Radionuclide Imaging; Technetium; Uterine Cervical Neoplasms

Technetium-99m-labeled pyrophosphate has proved to be a useful skeletal-imaging agent. In this study, specific areas of the skeleton were imaged at times ranging from 1/2 to 6 1/2 hr after injection of 99mTc-pyrophosphate. Count ratios between abnormal and normal bone with respect to adjacent soft tissue were obtained for selected regions of interest on computer-stored scintillation camera images. The results show that image quality improves most rapidly from 1/2 to 2 hr, but further modest gain in quality does occur on views recorded between 2 and 6 hr. All lesions detected on the later images were also observed on the early ones and the ratios of uptake between abnormal and normal bone from computer-processed scintillation camera images did not change appreciably with time after the 1/2-hr images. Our results confirm the clinical impression that overall image quality is better on views obtained at least 3 hr after injection. Further delays in imaging beyond 3-4 hr after injection probably will not result in any appreciable gain in diagnostic accuracy.

Topics: Bone Neoplasms; Diagnosis, Computer-Assisted; Diphosphates; Humans; Neoplasm Metastasis; Radionuclide Imaging; Technetium; Time Factors

Localization of 99mTc-pyrophosphate in the cardiac region during routine bone scanning for metastatic tumor is discussed in two cases. Clinical information as well as electrocardiographic and serum enzyme studies did not reveal any evidence of acute myocardial injury. The cause of myocardial localization of the radiopharmaceutical is not clear in these cases.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Carcinoma; Diphosphates; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myocardial Infarction; Myocardium; Neoplasm Metastasis; Radioisotopes; Technetium

99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age.

Topics: Age Factors; Aged; Bone Neoplasms; Breast Neoplasms; Diphosphates; False Positive Reactions; Humans; Joints; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Neoplasms; Radionuclide Imaging; Sarcoidosis; Technetium; Tin

Topics: Bone Neoplasms; Diphosphates; Female; Humans; Male; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Bone Neoplasms; Diphosphates; Etidronic Acid; Humans; Neoplasm Metastasis; Organophosphorus Compounds; Phosphates; Radionuclide Imaging; Technetium

Paralleled clinical studies of radioisotopic imaging or tumor metastases in the bone were undertaken with Tc99m pyrophosphate, Ga67 citrate, and Tc99m sulfur colloid. All three were capable of anticipating the bone roentgenograms. A critical analysis suggested that positive delineation with Ga67 citrate would sometimes be superior to the others. This deserves further investigation. Clinically the combined use of Tc99m pyrophosphate with Ga67 for the chest areas and extremties or with Tc99m colloid for the pelvic and abdominal areas would be more frutiful in early detection and exact localization of bone metastases.

Topics: Bone Neoplasms; Breast Neoplasms; Carcinoma, Squamous Cell; Citrates; Colloids; Diagnosis, Differential; Diphosphates; Esophageal Neoplasms; Humans; Leiomyosarcoma; Neoplasm Metastasis; Pancreatic Neoplasms; Radionuclide Imaging; Technetium

Various portions of the skeleton were examined in 125 patients both radiologically and by scanning, using 99mTc-pyrophosphate. The results are compared, particular attention being paid to errors in diagnosis. The figures show that scans represent a valuable additional form of examination for detecting tumours which have not been found radiologically. The importance of serial observations is discussed.

Topics: Bone Neoplasms; Diagnosis, Differential; Diagnostic Errors; Diphosphates; Extremities; False Negative Reactions; False Positive Reactions; Female; Humans; Male; Neoplasm Metastasis; Pelvis; Radiography; Radionuclide Imaging; Skull Neoplasms; Spinal Neoplasms; Technetium; Thoracic Neoplasms

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Drug Evaluation; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Drug Evaluation; Humans; Neoplasm Metastasis; Radionuclide Imaging; Technetium

Topics: Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Intestinal Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Phosphates; Radiography; Radionuclide Imaging; Technetium

Topics: Bone Neoplasms; Child; Child, Preschool; Diphosphates; Extremities; Facial Bones; Facial Neoplasms; Female; Fluorine; Gallium; Head and Neck Neoplasms; Humans; Iodine Radioisotopes; Male; Neoplasm Metastasis; Neuroblastoma; Radioisotopes; Radionuclide Imaging; Rhabdomyosarcoma; Skull Neoplasms; Strontium Isotopes; Technetium; Zygoma

Topics: Alkanes; Bone Neoplasms; Diphosphates; Humans; Neoplasm Metastasis; Organophosphonates; Phosphates; Radionuclide Imaging; Technetium

Topics: Aged; Bone Neoplasms; Diphosphates; Evaluation Studies as Topic; Humans; Male; Middle Aged; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Topics: Bone Marrow; Bone Neoplasms; Densitometry; Diphosphates; Humans; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radiation Dosage; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Arthritis; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Hodgkin Disease; Humans; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteolysis; Osteomalacia; Osteoporosis; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Rheumatic Diseases; Technetium; Tin

Topics: Adolescent; Adult; Aged; Bone Diseases; Bone Neoplasms; Child; Child, Preschool; Diphosphates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Technetium; Whole-Body Counting

Topics: Animals; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Carcinoma; Diphosphates; Humans; Lung Neoplasms; Male; Melanoma; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Rectal Neoplasms; Sodium; Technetium; Time Factors; Urinary Bladder Neoplasms

Topics: Arthritis, Infectious; Arthritis, Rheumatoid; Bone Diseases; Bone Neoplasms; Diphosphates; Drug Combinations; Humans; Joint Diseases; Male; Neoplasm Metastasis; Pelvic Neoplasms; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Topics: Alkaline Phosphatase; Cellulose; Cholelithiasis; Diphosphates; Electrophoresis; Hepatitis; Humans; Hyperparathyroidism; Hyperthyroidism; Intestinal Mucosa; Isoenzymes; Jejunum; Kidney Failure, Chronic; Kinetics; Liver; Liver Cirrhosis; Neoplasm Metastasis; Organ Specificity; Osteoporosis; Pyrophosphatases; Regression Analysis; Vinyl Compounds

Topics: Bone Neoplasms; Diphosphates; Humans; Metabolic Clearance Rate; Methods; Neoplasm Metastasis; Osteogenesis; Radionuclide Imaging; Statistics as Topic; Technetium; Tomography, X-Ray

Topics: Bone Neoplasms; Diphosphates; Humans; Neoplasm Metastasis; Radionuclide Imaging; Remission, Spontaneous; Strontium Radioisotopes; Technetium; Tomography, X-Ray

Topics: Bone Neoplasms; Chromatography, Paper; Diphosphates; Humans; Injections, Intravenous; Isotonic Solutions; Neoplasm Metastasis; Radionuclide Imaging; Sodium; Technetium; Technology, Radiologic; Tibia

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Bone Neoplasms; Carcinoma 256, Walker; Child; Child, Preschool; Diphosphates; Female; Humans; Hydroxyproline; Male; Middle Aged; Neoplasm Metastasis; Rats