PubMed_ArguminSci  

PubMed:30843003 JSONTXT 7 Projects

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Id Subject Object Predicate Lexical cue
T1 115-183 DRI_Background denotes ancer (PCa) is the most common solid cancer affecting men worldwide.
T2 184-363 DRI_Background denotes Serum prostate-specific antigen (PSA) is at present the most commonly used biomarker for PCa screening, as well as a reliable marker of disease recurrence after initial treatment.
T3 432-612 DRI_Background denotes Imaging of BM is important not only for localization and characterization, but also to evaluate their size and number, as well as to follow-up the disease during and after therapy.
T4 613-758 DRI_Background denotes Bone metastases formation is triggered by cancer initiating cells in the bone marrow and is facilitated by the release of several growth factors.
T5 759-905 DRI_Outcome denotes Although BM from PCa are very heterogenic, the majority of them are described as "osteoblastic", while pure "osteolytic" metastases are very rare.
T6 906-987 DRI_Approach denotes The PSA levels, along with other parameters, may determine the risk of having BM.
T7 1338-1558 DRI_Outcome denotes Even though PSA remains the only biomarker of this disease in clinical practice, it is not always analogue with the severity of the disease and should be evaluated along with the clinical and diagnostic imaging findings.
T8 1559-1650 DRI_Challenge denotes Detection of BM is not always easy, as there may be unexpected sites and occult metastases.
T9 1651-1839 DRI_Challenge denotes The clinical importance of revealing BM in patients with PCa is to determine the overall survival of the patients and their quality of life, as BM may lead to high morbidity and mortality.
T10 1840-2040 DRI_Background denotes There are many options of treating BM, such as chemotherapy, immunotherapy, external beam radiotherapy, bone modifying agents and recently prostate-specific membrane antigen (PSMA) targeted therapies.
T11 2041-2144 DRI_Background denotes Another potential therapy is radioguided surgery, in patients with occult and/or focally recurrent PCa.
T12 2145-2279 DRI_Background denotes Such a single occult metastasis causing very high levels of PSA has been presented using technetium-99m (99m Tc) labeled PSMA imaging.
T13 2280-2515 DRI_Background denotes Diagnosis and staging of PCa mostly relies on the morphology of imaging, using computerized tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/CT (PET/CT) using fluorine-18-fluorodeoxyglucose (18 F-FDG).
T14 2516-2806 DRI_Approach denotes The radiopharmaceuticals used in Nuclear Medicine for BM in PCa are: a) those that target lesions, such as 99m Tc-phosphonates, 18 F-sodium fluoride (18 F-NaF) and b) those that target the cancer cells, such as 18 F or carbon-11 (11 C)-choline, 18 F-FDG and 18 F or gallium-68 (68 Ga)-PSMA.
T15 2807-2915 DRI_Background denotes Bone scan with 99mTc-phosphonates is widely used for the evaluation of bone metabolism in patients with PCa.
T16 2916-3019 DRI_Approach denotes It is a low cost, widely available radiopharmaceutical having the advantage of a whole body evaluation.
T17 3020-3092 DRI_Background denotes Planar and single photon emission tomography (SPET) may also be applied.
T18 3093-3334 DRI_Outcome denotes The sensitivity of the whole body scan (WBS) ranges from 75%-95%, while the specificity is lower, ranging from 60%-75% due to false positive findings in benign conditions (arthritis, inflammation etc) who also have increased bone metabolism.
T19 3335-3459 DRI_Background denotes Sensitivity and specificity however, perform better (96% and 94% respectively) when SPET and SPET/CT techniques are applied.
T20 3460-3522 DRI_Approach denotes Of course, bone marrow metastases cannot be detected in a WBS.
T21 3523-3779 DRI_Approach denotes The PSA marker is used to predict the pre-test probability of BM and in case of a bone scan several retrospective analyses showed that PSA levels <20ng/mL can exclude with high probability a positive WBS, with a high negative predictive value (almost 99%).
T22 3780-3936 DRI_Approach denotes The European Association of Urology (EAU) guidelines state that a bone scan can be omitted in patients with PSA levels <20ng/mL and with a Gleason Score ≤7.
T23 3937-3952 DRI_Background denotes Imaging with 18
T24 3966-4170 DRI_Background denotes is characterized by high and rapid bone uptake, minimal serum protein binding and rapid blood clearance which lead to a fast and high target to background ratio with a short acquisition time (30 minutes).
T25 4171-4264 DRI_Outcome denotes Sensitivity and specificity for the detection of BM in high risk PCa patients is almost 100%.
T26 4265-4299 DRI_Outcome denotes The main advantages provided by 18
T27 4313-4405 DRI_Outcome denotes are the better imaging quality along with a whole body acquisition and the fusion technique.
T28 4406-4432 DRI_Background denotes Fluorine-18-choline and 11
T29 4450-4515 DRI_Background denotes came to practice lately, reflecting the cell membrane metabolism.
T30 4516-4639 DRI_Background denotes Choline is an essential component of phospholipids and is trapped in the cells after a phosphorylation by a choline kinase.
T31 4640-4677 DRI_Outcome denotes The sensitivity and specificity of 18
T32 4695-4776 DRI_Outcome denotes for detecting BM in patients with PCa is reported to be 79% and 97% respectively.
T33 4777-5023 DRI_Outcome denotes However, the performance of choline PET/CT seems to be dependent of the levels of the PSA, in cases of biochemical recurrence and reaches about 75%% in those PCa patients with PSA levels >3ng/mL, with a poor performance when the PSA level is low.
T34 5024-5148 DRI_Background denotes Fluorine-18-FDG is the most commonly used radiotracer in PET/CT, however has a little value in staging and restaging of PCa.
T35 5149-5375 DRI_Background denotes Because of its low sensitivity 18 F-FDG is trapped in cancer cells through the activation of the glycolytic pathways and in case of BM is an index of increased glucose metabolism in PCa cells rather than in bone lesion per se.
T36 5376-5501 DRI_Outcome denotes Osteolytic lesions show more increased metabolic activity than the osteoblastic lesions and are better revealed with 18F-FDG.
T37 5502-5515 DRI_Background denotes Therefore, 18
T38 5529-5651 DRI_Background denotes is suggested to be performed only in selected patients with PCa, those with most aggressive tumors and high Gleason score.
T39 5652-5668 REPLACED denotes Fluorine-18-PSMA
T40 5676-5741 DRI_Approach denotes The need of a more sensitive and specific agent has been evident.
T41 5742-5835 DRI_Background denotes Prostate specific monoclonal antibody (PSMA) is a folate hydrolase cell surface glycoprotein.
T42 5836-6037 DRI_Background denotes It is mainly expressed in four tissues of the body, including prostate epithelium, the proximal tubules of the kidney, the jejunal brush border of the small intestine and ganglia of the nervous system.
T43 6038-6140 DRI_Outcome denotes So consequently may in some cases be expressed in cancers other than PCa and also in benign processes.
T44 6141-6248 DRI_Approach denotes It is localized in the cytoplasm and the apical side of the prostate epithelium that lines prostatic ducts.
T45 6249-6403 DRI_Background denotes In case of malignant transformation, PSMA is transferred from the cytoplasm to the luminal surface of the prostatic ducts and thus becomes membrane bound.
T46 6404-6526 DRI_Background denotes It has a unique three-parts structure, an external portion, a transmembrane portion and an internal-cytoplasmatic portion.
T47 6527-6669 DRI_Background denotes Prostate specific monoclonal antibody is also upregulated and thus overexpressed in most PCa, but weakly expressed in normal prostatic tissue.
T48 6670-6680 DRI_Background denotes Imaging by
T49 6693-6792 DRI_Background denotes has been shown to detect sites of disease recurrence at lower PSA levels than conventional imaging.
T50 6793-6949 DRI_Challenge denotes The PSMA overexpression is even present when the cell becomes castrate-resistant and that is the reason why it is the most favorable target for PET imaging.
T51 6950-7118 DRI_Background denotes Prostate cancer expresses 100 to 1000 times more PSMA than normal tissue and is increasing even more in higher grade tumors as well as in increased castrate resistance.
T52 7119-7222 DRI_Approach denotes Therefore, PSMA represents an excellent target for both diagnostic imaging and endoradiotherapy of PCa.
T53 7223-7503 DRI_Background denotes For diagnostic purposes PSMA ligands, mainly small-molecule inhibitors, are most commonly labeled either with 68 Ga or 18 F. The 18 F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18 F-fluoronicotinamido) butanamido) methyl phenyl)-3- (naphthalen-2-ylmethyl)
T54 7571-7758 DRI_Background denotes acid)) seems to be more favorable among other 18 F-PSMA ligands candidate compounds because it demonstrates high labeling yields, better tumor uptake and non-urinary background clearance.
T55 7759-7908 DRI_Background denotes On the contrary, 68 Ga-PSMA is rapidly excreted via the urinary tract resulting in intense accumulation in the bladder, thus, obscuring the prostate.
T56 7909-8062 DRI_Outcome denotes Compared to 68 Ga, 18 F has many advantages such as it is produced in larger amounts, it has a longer half life and a higher physical spatial resolution.
T57 8063-8320 DRI_Approach denotes The short half-life of 68 Ga relative to 18 F (68 vs. 110 min) makes 68 Ga-PSMA inconvenient for longer transport, so that it is almost mandatory to use local gallium generators, which have a higher cost and lower yields at the end of their first half-life.
T58 8321-8468 DRI_Approach denotes Each generator provides only one or two elutions per day and it requires separate syntheses at different times of the day in a local radiopharmacy.
T59 8469-8578 DRI_Outcome denotes Furthermore, the resolution of 68 Ga-labeled tracers is physically limited because of positron range effects.
T60 8579-8696 DRI_Background denotes In contrast, 18 F labels avoid these intrinsic difficulties and can be produced at high yields in central cyclotrons.
T61 8697-8958 DRI_Outcome denotes Fluorine-18-PSMA-1007 has been recently used by us in the Nuclear Medicine Department of "Evangelismos" general hospital of Athens and our experience so far showed favorable results, with high image resolution acquisitions and lesions which showed PSMA avidity.
T62 8959-8980 REPLACED denotes Fluorine-18-PSMA-1007
T63 8988-9073 DRI_Approach denotes imaging was carried out with a dual phase protocol, consisting of two separate scans.
T64 9074-9245 DRI_Background denotes One (early scan) at 60min post injection starting from the diaphragm to the middle of the thighs and the late scan at 180min from the dome of the skull to the knee joints.
T65 9246-9298 DRI_Background denotes Patients were asked to urine before the examination.
T66 9299-9502 DRI_Approach denotes Images were acquired with a scan time of 3min per bed position on a General Electric PET/CT system and the image reconstruction was performed by the standard software method provided by the manufacturer.
T67 9503-9634 DRI_Approach denotes A low dose CT scan, without a contrast agent, was performed before the PET scan in order to be used for the attenuation correction.
T68 9635-9757 DRI_Approach denotes Administered activities were calculated based on the department's protocols with a suggested injected activity of 4MBq/kg.
T69 9758-9948 DRI_Outcome denotes Any areas of focally increased radiotracer uptake, at both the early and late PET scans, were considered as abnormal, despite the presence or absence of morphological changes of the CT scan.
T70 9949-10272 DRI_Background denotes The normal distribution of the radiotracer was taken under consideration, which includes mainly the liver and the gallbladder, as it has hepatobiliary clearance rather than renal, the spleen, the pancreas, the submandibular, sublingual, lacrimal and parotid glands, the kidneys, the urinary bladder and the small intestine.
T71 10273-10351 DRI_Approach denotes The maximum standardized uptake value (SUVmax) was calculated for each lesion.
T72 10352-10500 DRI_Approach denotes A typical case of a 78 years man with PCa having PSA 7,3ng/mL and also having Paget's disease was tested by the above procedure for initial staging.
T73 10501-10507 DRI_Background denotes The 18
T74 10527-10626 DRI_Background denotes imaging revealed diffusely increased radiotracer uptake in the bones of the pelvis with a SUVmax 9.
T75 10627-10783 DRI_Outcome denotes The CT imaging of the pelvis was consistent with Paget's disease, with diffuse mixed osteosclerotic and osteolytic lesions, accompanied with bone expansion.
T76 10784-11022 DRI_Outcome denotes The primary PCa was also revealed with focally increased radiotracer uptake in the left prostatic lobe with a SUVmax 19, as well as a second small focus of pathologically increased PSMA uptake in the right prostatic lobe with a SUVmax 23.
T77 11023-11081 DRI_Background denotes Another patient 79 years old, with PCa was studied with 18
T78 11099-11150 DRI_Background denotes which showed diffuse bone metastasis in the pelvis.
T79 11179-11185 DRI_Outcome denotes The 18
T80 11205-11375 DRI_Outcome denotes imaging showed multiple foci of increased radiotracer uptake throughout the whole skeleton, including the skull, both humerus and femoral bones with indicative SUVmax 26.
T81 11376-11421 DRI_Background denotes Computed tomography showed rather similar BM.
T82 11422-11549 DRI_Approach denotes There were also lymph nodes metastases at the left internal mammary chain as well as the left inguinal areas, with a SUVmax 25.
T83 11550-11582 DRI_Outcome denotes The first case indicated that 18
T84 11597-11756 DRI_Outcome denotes could easily differentiate PCa BM from Paget's disease, however benign conditions such as Paget's disease may also show PSMA uptake and the second case that 18
T85 11771-11806 DRI_Outcome denotes scan was more sensitive than the 18
T86 11824-11855 DRI_Outcome denotes scan, with high quality images.
T87 11856-11941 DRI_Background denotes According to other authors the SUVmax value of BM in PCa was 16.57±23.59 using the 18
T88 11956-11961 DRI_Background denotes scan.
T89 11962-12032 DRI_Background denotes This imaging modality in accordance to other authors is better than 68
T90 12058-12113 DRI_Background denotes and can better differentiate BM from healing fractures.
T91 12114-12280 DRI_Background denotes Very recently a novel PET radiopharmaceutical has been approved both in USA and Europe: 18 F-fluciclovine (trans-1-amino-3-[18 F] fluoro-cyclobutane carboxylic acid).
T92 12281-12450 DRI_Background denotes Fluorine-18-fluciclovine is a synthetic amino acid that is transported by multiple sodium-dependent and sodium-independent channels found to be upregulated in PCa cells.
T93 12451-12590 DRI_Approach denotes The main indication of use includes the detection and localization of PCa recurrence in patients with a rising PSA following prior therapy.
T94 12591-12760 DRI_Outcome denotes The main advantages of 18 F-fluciclovine are the low urinary excretion, which allows for better evaluation of prostate bed and the low uptake in inflammatory cells (e.g.
T95 12775-13004 DRI_Background denotes There are no studies in the literature comparing 18 F-PSMA to 18 F-fluciclovine, however two studies comparing 18 F-fluciclovine to 68 Ga-PSMA, showed better performance for 68 Ga-PSMA in PCa patients with biochemical recurrence.
T96 13005-13011 DRI_Background denotes So, 18
T97 13031-13169 DRI_Background denotes imaging seems to be very promising in staging and restaging patients with PCa, especially when biochemical relapse is under consideration.
T98 13170-13254 DRI_Challenge denotes Although it seems to perform better than other imaging modalities like bone scan, 18
T99 13268-13273 DRI_Challenge denotes or 18
T100 13290-13346 DRI_Challenge denotes , its high cost and low availability must be considered.
T101 13347-13497 DRI_Approach denotes Further large studies need to be conducted in order to evaluate the accuracy and the predictive values of this method, emphasizing on bone metastases.