pyrophosphate and Lung-Neoplasms

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

Detection of EGFR mutations in circulating cell-free DNA (cfDNA) is beneficial to monitor the therapeutic effect, tumor progression, and drug resistance in real time. However, it requires that the mutation detection method has the ability to quantify the mutation abundance accurately. Although the next-generation sequencing (NGS) and digital PCR showed high sensitivity for quantifying mutations in cfDNA, the use of expensive equipment and the high-cost hampered their applications in the clinic. Herein, we propose a highly sensitive and specific real-time PCR by employing serial invasive reaction as a sequence identifier for quantifying EGFR mutation abundance in cfDNA (termed as qPCR-Invader). The mutation abundance can be quantified by using the difference of Ct values between mutant and wild-type targets without the need of making a standard curve. The method can quantify a mutation level as lower as 0.1% (10 copies/tube). Thirty-six tissue samples from non-small-cell lung cancer (NSCLC) patients were detected by our method and 14/36 tissues gave EGFR L858R mutation-positive results, whereas ARMS-PCR just identified 12 of L858R mutant samples. The two inconsistent samples were confirmed as L858R mutant by pyrophosphorolysis-activated polymerization method, indicating that qPCR-Invader is more sensitive than ARMS-PCR for mutation detection. The L858R mutation abundances of 19 cfDNA samples detected by qPCR-Invader were close to that from NGS, indicating our method can precisely quantify mutation abundance in cfDNA. The qPCR-Invader just needs a common real-time PCR device to accomplish quantification of EGFR mutations, and the fluorescence probes are universal for any target detection. Therefore, it could be used in most laboratories to analyze mutations in cfDNA. Graphical abstract ᅟ.

Topics: Base Sequence; Carcinoma, Non-Small-Cell Lung; Cell-Free Nucleic Acids; Diphosphates; ErbB Receptors; Fluorescence; High-Throughput Nucleotide Sequencing; Humans; Limit of Detection; Lung Neoplasms; Mutation; Polymerization; Real-Time Polymerase Chain Reaction; Reproducibility of Results

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

Human tuberculosis is a chronic infectious disease affecting millions of lives. Because of emerging resistance to current medications, new therapeutic drugs are needed. One potential new target is hypoxanthine-guanine phosphoribosyltransferase (MtHGPRT), a key enzyme of the purine salvage pathway. Here, newly synthesized acyclic nucleoside phosphonates (ANPs) have been shown to be competitive inhibitors of MtHGPRT with Ki values as low as 0.69 μM. Prodrugs of these compounds arrest the growth of a virulent strain of M. tuberculosis with MIC50 values as low as 4.5 μM and possess low cytotoxicity in mammalian cells (CC50 values as high as >300 μM). In addition, the first crystal structures of MtHGPRT (2.03-2.76 Å resolution) have been determined, three of these in complex with novel ANPs and one with GMP and pyrophosphate. These data provide a solid foundation for the further development of ANPs as selective inhibitors of MtHGPRT and as antituberculosis agents.

Topics: Amino Acid Sequence; Antineoplastic Agents; Antitubercular Agents; Catalytic Domain; Cell Proliferation; Crystallography, X-Ray; Diphosphates; Enzyme Inhibitors; Guanosine Monophosphate; Humans; Hypoxanthine Phosphoribosyltransferase; Lung Neoplasms; Models, Molecular; Molecular Sequence Data; Molecular Structure; Mycobacterium tuberculosis; Organophosphonates; Prodrugs; Protein Conformation; Sequence Homology, Amino Acid; Structure-Activity Relationship; Tuberculosis; Tumor Cells, Cultured

Radionuclide bone scans were performed before and during combination chemotherapy in 119 systematically staged patients with small cell carcinoma of the lung. Before therapy, 49 patients (41%) had positive scans. Scan positivity was significantly associated with the presence of metastatic tumor in the bone marrow, positive skeletal radiographs, and elevated serum alkaline phosphatase levels. Nonosseous distant metastases were significantly more likely to be detected as the number of areas of focal abnormalities on bone scan increased. The survival of patients with documented distant metastases in bone and nonosseous sites was significantly inferior to the survival of patients with limited disease, isolated osseous extensive disease, and extensive disease occurring only in nonbony sites. Of 36 patients with initially abnormal scans and tumor regression documented by other methods, scan findings improved in 24 (67%). In 26 (36%) of 72 scans in patients demonstrating disease progression in extraosseous sites, new areas of increased radionuclide uptake appeared. Improvement or worsening in follow-up scans was associated with nonbony tumor response or progression, respectively, 70% of the time. Serial bone scans provide reasonably accurate staging and prognostic information in patients with small cell lung cancer, although they are probably not sufficiently reliable to be used as the sole parameter in therapeutic decision-making.

Topics: Antineoplastic Agents; Bone Neoplasms; Carcinoma, Small Cell; Diphosphates; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Lung Neoplasms; Prognosis; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Aged; Carcinoma, Bronchogenic; Diphosphates; Humans; Lung Neoplasms; Male; Pericardial Effusion; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

A case of small cell anaplastic carcinoma of the lung with hepatic secondaries has been found to accumulate Tc-99m-pyrophosphate in both lung primary and hepatic metastases and to our knowledge is the first such case reported in the literature. There was no radiographic evidence of calcification in the tumor or hepatic metastases.

Topics: Aged; Bone and Bones; Diphosphates; Humans; Liver Neoplasms; Lung Neoplasms; Male; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

A case of radiation pneumonitis confirmed by tissue biopsy is presented with demonstration of increased uptake of 99mTc-pyrophosphate.

Topics: Adult; Diphosphates; Female; Humans; Lung Diseases; Lung Neoplasms; Necrosis; Radiation Injuries; Radionuclide Imaging; Radiotherapy; 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

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

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

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

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: 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