pyrophosphate and Breast-Neoplasms

Topics: Angina Pectoris; Angina, Unstable; Animals; Breast Neoplasms; Cardiomyopathies; Coronary Disease; Diagnosis, Differential; Diphosphates; Dogs; Electric Countershock; Humans; Myocardial Infarction; Radionuclide Imaging; Rats; Rib Fractures; Technetium; Technetium Tc 99m Pyrophosphate

Bone scanning is a sensitive test for the detection of metastatic breast cancer, but not all abnormal findings on bone scan are diagnostic of skeletal metastasis. Recent studies have found a relatively low rate (less than or equal to 5%) of abnormal scans in patients with Stage I and II breast cancers, and only half of those with positive scans subsequently had documented bony metastasis. The overwhelming clinical experiences summarized here question the value of including bone scanning as part of the routine work-up of patients with early breast cancers.

Topics: Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; False Negative Reactions; False Positive Reactions; Female; Fluorine; Humans; Neoplasm Staging; Prognosis; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Bone and Bones; Bone Neoplasms; Breast Neoplasms; Carcinoma; Diphosphates; Diphosphonates; Fractures, Bone; Humans; Lung Neoplasms; Male; Osteomyelitis; Prostatic Neoplasms; Radionuclide Imaging; Technetium; Technetium Compounds; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

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

From 1977 to 1987, 7,604 out of a total of 20,483 Danish breast cancer patients had a bone scintigraphy in order to exclude or localise osseous metastases. The scintigrams were performed and interpreted at 14 local hospitals. In 1979, standardised guidelines for interpretation were agreed upon. Until 1983, the scintigrams were described centrally, based on the local reports. From 1979, the frequency of positive bone scintigrams suggesting bone metastases stabilised at about 5% of the patients compared with 12 and 20% in 1977-78. The local take-over of description did not change the frequency. The frequency was also stable from 1979 when evaluated in age groups. With increasing age the frequency of positive scintigrams increased. The frequency of positive scintigrams was significantly lower in patients entering a protocol than in those not entering a protocol. The conclusion is that on a nation-wide basis it is possible to establish a stable, uniform interpretation of bone scintigrams after a two-year introduction period.

Topics: Adult; Age Factors; Aged; Bone Neoplasms; Breast Neoplasms; Diagnosis, Differential; Diphosphates; Female; Humans; Intraoperative Period; Middle Aged; Multicenter Studies as Topic; Polyphosphates; Radionuclide Imaging; Technetium; Technetium Compounds; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate; Time Factors

Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation.

Topics: Adenosine Diphosphate Ribose; Adenosine Triphosphate; Breast Neoplasms; Cell Nucleus; Cell Proliferation; Chromatin Assembly and Disassembly; Crystallography, X-Ray; Diphosphates; Energy Metabolism; Female; Gene Expression Regulation; Humans; Hydrolysis; MCF-7 Cells; Poly (ADP-Ribose) Polymerase-1; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerases; Progestins; Protein Multimerization; Pyrophosphatases

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

A scintigraphic picture was observed in 51 patients suffering from breast cancer with metastatic involvement of the skeleton (polychemotherapy + radiotherapy of pelvic bones and lumbar spine + hormonotherapy) to determine the role of scintigraphy in the assessment of therapeutic effectiveness. According to scintigraphic signs of changes in RP accumulation in metastases the following groups were singled out: a complete effect, a partial effect, stabilization, progression of disease. The mean interval from the onset of therapy up to the appearance of scintigraphic signs of a therapeutic effect was 8.6 mos. A high degree of correlation between scintigraphic signs of a therapeutic effect and the time course of the pain syndrome in the skeletal bones was shown.

Topics: Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Diphosphates; Female; Humans; Middle Aged; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

A case of severe hypercalcemia due to metastases to bone from a primary breast cancer is presented. The different drugs available for treating hypercalcemia are described, and the rationale for their use is discussed.

Topics: Bone Neoplasms; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Diphosphates; Drug Therapy, Combination; Female; Humans; Hypercalcemia; Middle Aged; Plicamycin

The objective of this study is to correlate the presence of bone and liver metastases in patients with breast cancer with respect to the results of bone and liver scans, axillary nodal status, and serum alkaline phosphatase levels. One hundred ninety-seven patients with breast cancer treated by modified radical mastectomy between the years 1978 and 1981 were studied. Fifty-nine (30%) of the total group had distant metastases during the course of observation of 60 to 96 months; of 35 patients in whom bone metastases developed, 30 had normal preoperative bone scan results. Of 21 patients who had liver metastases, 19 had normal preoperative liver scans. Nineteen (70%) of the 27 patients with abnormal bone scans had normal alkaline phosphatase levels. Seven (63%) of the 11 patients who had abnormal liver scans had a normal alkaline phosphatase. The study supports the concept that preoperative bone and liver scans are ineffective indicators of metastatic involvement. Selection of patients for screening by bone and liver scans according to alkaline phosphatase determinations was not supported by this study. The appropriate use of bone scans for screening in patients with breast carcinoma is suggested as a follow-up device in patients with positive lymph nodes.

Topics: Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Liver Neoplasms; Mastectomy; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate; Technetium Tc 99m Sulfur Colloid

The paper is concerned with the results of radionuclide investigation of 51 patients with different tumors located beyond the osseous tissue. In spite of the fact that 99mTc-phosphates were well known as agents for radionuclide diagnosis of bone tumors, they can be employed for obtaining certain diagnostic information concerning topical diagnosis and the determination of a degree of the distribution of processes of nonskeletogenous nature. Of 51 patients with soft tissue pathology clear visualization of lesion foci was obtained in 34 patients (66.7%). Positive results of radionuclide diagnosis with 99mTc-pyrophosphate were noted in scintigraphy of patients with breast, ovarian, soft tissue and maxillofacial tumors. Besides, clear visualization of lesion foci was achieved in 6 of 11 patients with benign diseases: postoperative scars, inflammatory infiltrates, synovioma. The results obtained indicated the absence of necessary specificity of 99mTc-phosphates to osseous tissue.

Topics: Breast Neoplasms; Diphosphates; Facial Neoplasms; Female; Genital Neoplasms, Female; Humans; Radionuclide Imaging; Soft Tissue Neoplasms; Spinal Cord Neoplasms; Technetium; Technetium Tc 99m Pyrophosphate

As for the frequency of metastases to the bones breast cancer ranks third among all tumors, as for the general frequency of metastases it ranks first (25-45%). Early diagnosis of breast cancer metastases to the bones using scintigraphy of the skeleton in the preoperative period gives an opportunity to reveal tumor dissemination and to provide adequate treatment without imposing on patients inappropriate therapeutic measures. The study was performed using 99mTc-pyrophosphate. In revealing the foci of high activity accumulation by more than 20% as compared to symmetrical or adjacent zones, the changes were looked upon as metastatic ones. Out of 85 patients foci of high activity accumulation in the skeleton were noted in 7 (8.3%). In 5 patients, metastases were confirmed directly on roentgenography, and in 2 patients, they manifested themselves 2 and 5 months later. Stage I-IIa disease was observed in 48 (56.5%) out of the 85 patients. Out of the 40 patients with Stage I disease, skeletal metastases confirmed by x-ray were found in 2. All 7 patients were given together with mastectomy adjuvant treatment. Thus scintigraphy of the skeleton together with chest x-ray, liver scintigraphy, physical examination and palpation should become obligatory in the preoperative examination of patients to specify breast cancer stage.

Topics: Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Neoplasm Staging; Preoperative Care; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; Diphosphonates; Female; Follow-Up Studies; Humans; Middle Aged; Radionuclide Imaging; Technetium; Technetium Compounds; Technetium Tc 99m Pyrophosphate

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Middle Aged; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Eight patients with persistent pain due to disseminated bone metastases from mammary carcinoma were given about 370 MBq (10 mCi) of 32P-pyrophosphate on 10 occasions. All but one of the patients experienced alleviation of pain lasting 1 to 4 months. The side effects, which derived mainly from haematopoetic tissue, prevent the routine use of this compound.

Topics: Blood Cell Count; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Male; Palliative Care; Phosphorus Radioisotopes

Extraskeletal uptake of tracer, presumably in the lymph nodes, is an uncommon finding in bone scans. It has been seen only when there is extravasation of tracer at the injection site. The phenomenon appears to be the result of colloid formation.

Topics: Bone and Bones; Breast Neoplasms; Diphosphates; Female; Humans; Lymph Nodes; Radionuclide Imaging; Technetium

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Humans; Middle Aged; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

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

Of 70 consecutive cancer patients referred from radiotherapy for bone scans, 32% showed cardiac uptake of 99mTc-(Sn)-pyrophosphate; only 9% of a control group showed this uptake. Of those with prior left hemithorax irradiation, 60% showed cardiac uptake; only 12% of those with irradiation elsewhere showed this phenomenon (p less than .01). The patients who had no increased uptake tended to have shorter irradiation-to-scan time intervals (less than 10 months) than those who did show increased uptake (mean of 22 months).

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Diphosphates; Female; Hodgkin Disease; Humans; Lung Neoplasms; Male; Middle Aged; Myocardium; Radionuclide Imaging; Radiotherapy; Technetium; Thorax

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

The concentration of 99mTc-pyrophosphate was determined in the lower extremities of rabbits (normal, abacterial and bacterial affected soft tissues), in osteoarthritis of the hip joint (capsule and muscle) as well as in knee joint effusions. Compared with the 85Sr-concentration, reflecting the calcification capacity, concentrations of 99mTc-pyrophosphate in soft tissues were found to be lower 2 hours p.i., but were up to elevenfold higher 24 hours p.i. These findings should be due to a fixation of 99mTc-pyrophosphate in collagen containing tissues as in the soft tissue tumors (myosarcoma, synvialioma, breast cancer) presented. A mechanism of delayed equilibration could explain augmented uptake in lymph-edema, ascites and effusions in florid osteoarthritis of the knee joint. The possible dependence of 99mTc-pyrophosphate concentration in bone and soft tissue on collagenous contents is discussed.

Topics: Animals; Ascites; Bone and Bones; Breast Neoplasms; Diphosphates; Disease Models, Animal; Extremities; Freund's Adjuvant; Hip; Humans; Joint Diseases; Joint Prosthesis; Joints; Knee; Osteoarthritis; Phosphates; Rabbits; Rhabdomyosarcoma; Sarcoma, Synovial; Strontium; Strontium Radioisotopes; Technetium; Tibial Fractures; Time Factors; Tin

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

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

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

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: Ankle Joint; Arthritis, Rheumatoid; Bone and Bones; Breast Neoplasms; Diphosphates; Female; Humans; Kinetics; Knee Joint; Male; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Rheumatic Fever; Spondylitis, Ankylosing; Strontium Radioisotopes; Technetium; Whole-Body Counting