Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[(11)C]Choline has been under investigation as a PET ligand for imaging tumor tissue, especially prostate cancer. An improved, automated synthesis of the tracer now was established. [(11)C] Choline was produced by labeling 2-(dimethylamino)-ethanol (DMAE) with [(11)C]CH(3)I in a Tefzel tube at room temperature without solvent. The product was purified using a cation exchange cartridge. Reaction conditions were optimized with respect to synthesis time and amount of DMAE, resulting in radiochemical yields higher than 80% using 60 microl of DMAE in 20 min, radiochemical purity was >99% and residual DMAE was below 10 ppm. After (11)C-production of 1h at 50 microA [(11)C]choline activities of 30.0+/-5.6 GBq (n = 29) were obtained in sterile solution ready for intravenous administration.
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PMID:Highly efficient automated synthesis of [(11)C]choline for multi dose utilization. 1511 Mar 47

[(11)C]Choline has been evaluated as a positron emission tomography (PET) biomarker for assessment of established human prostate cancer tumor models. [(11)C]Choline was prepared by the reaction of [(11)C]methyl triflate with 2-dimethylaminoethanol (DMAE) and isolated and purified by solid-phase extraction (SPE) method in 60-85% yield based on [(11)C]CO(2), 15-20 min overall synthesis time from end of bombardment (EOB), 95-99% radiochemical purity and specific activity >0.8 Ci/micromol at end of synthesis (EOS). The biodistribution of [(11)C]choline was determined at 30 min post iv injection in prostate cancer tumor models C4-2, PC-3, CWR22rv, and LNCaP tumor-bearing athymic mice. The results showed the accumulation of [(11)C]choline in these tumors was 1.0% dose/g in C4-2 mouse, 0.4% dose/g in PC-3 mice, 3.2% dose/g in CWR22rv mice, and 1.4% dose/g in LNCaP mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 2.3 (T/M, C4-2), 1.4 (T/M, PC-3), 2.5 (T/M, CWR22rv), 1.2 (T/M, LNCaP) and 2.6 (T/B, C4-2), 2.6 (T/B, PC-3), 7.8 (T/B, CWR22rv), 3.2 (T/B, LNCaP), respectively. The micro-PET imaging of [(11)C]choline in prostate cancer tumor models was acquired from a C4-2, PC-3, CWR22rv, or LNCaP implanted mouse at 30 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, IndyPET-II scanner, developed in our laboratory, which showed the accumulation of [(11)C]choline in C4-2, PC-3, CWR22rv, or LNCaP tumor implanted in a nude athymic mouse. The initial dynamic micro-PET imaging data indicated the average T/M ratios were approximately 3.0 (C4-2), 2.1 (PC-3), 3.5 (CWR22rv), and 3.3 (LNCaP), respectively, which showed the tumor accumulation of [(11)C]choline in all four tumor models is high. These results suggest that there are significant differences in [(11)C]choline accumulation between these different tumor types, and these differences might offer some useful measure of tumor biological process.
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PMID:[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models. 1514 49

The diagnosis of prostate cancer leaves some questions without answers. The different diagnostic techniques are limited in three situations: (1) staging of the tumour: identification of node involvement, (2) quantification of the tumour volume and its location inside the gland, (3) premature identification of relapse after radical treatment. These are the three problems that we need to consider in the diagnosis of prostate carcinoma. Imaging techniques can tell us the morphological alterations in the structures and organs. Positron emission tomography (PET) introduces a new way of identifying damage by counting metabolic activity. The tracers are substances that are marked with a radioactive molecule that is picked up more readily by the tumours. The presence of these substances in a set anatomic zone means higher consumption and therefore more metabolic activity. The radiotracer most frequently used in PET is glucose marked with fluoride 18. The first studies with marked glucose and prostate tumours started at the end of the 1990s. There are many contradictions in the results of these studies due to renal elimination, which produces an accumulation in the urinary tract and does not correctly show the prostate zone and iliobturator nodes area, and its capitation by zones with inflammatory process or prostatic hyperplasia. Choline is a substance that is present in cellular membranes. When it is marked with carbon 11, it changes to a new tracer. This radiotracer has affinity with prostate damage and allows the better differentiation of malignant from benign processes. It also has the advantage of the absence of renal elimination. Trials that used choline marked with carbon 11 (11C choline) are beginning to obtain very promising results. This union of a method that identifies metabolic activity with an imaging technique increases the sensitivity in the diagnostic test and can help find the exact location of the 11C choline deposits. The PET-CT combines the PET with computerised tomography. The 11C choline PET-CT is presented as a promising technique for answering the three problems mentioned above.
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PMID:PET and prostate cancer. 1550 49

Prostate cancer is the most common malignant disease and second in causes of cancer death among men in Western Europe and North America. Despite improved surgical and irradiation techniques tumor relapse after curatively intended therapy is not uncommon. Due to the difficulty in discriminating local and systemic progression, it is often difficult to decide what this means for the patient and what kind of second-line treatment has to be given. Modern imaging techniques (MRI with endorectal coil, Choline-PET-CT, ProstaScint-Scan) are used for diagnosis of prostate cancer relapse. Nevertheless, early detection of local tumor relapse and likewise the detection of disseminated tumor cells often fails. To differentiate between local and systemic progression, prognostic factors of the primary tumor (grading, surgical margins, infiltration of the seminal vesicles, lymph node metastases) and PSA kinetics are used. The time from initial treatment to biochemical relapse and PSA doubling time are of highest prognostic relevance. Local progression allows second-line local treatment with potentially curative results (local irradiation after radical prostatectomy, salvage-surgery / cryotherapy / HIFU after irradiation), while in the case of systemic progress a palliative systemic therapy (hormonal treatment, chemotherapy, bisphosphonates) is indicated. Before deciding on the most appropriate therapy, prognostic factors and the patient's individual situation (co-morbidity, life expectancy, individual wishes) should be taken into account.
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PMID:Prostate cancer relapse after therapy with curative intention: a diagnostic and therapeutic dilemma. 1593 26

Abnormalities of choline processing in cancer cells have been used as a basis for imaging of cancer with positron emission tomography and magnetic resonance spectroscopy. In this study, the transport mechanism for choline was investigated in cultured PC-3 prostate cancer cells. Furthermore, tritiated hemicholinium 3 (HC-3), a well-known inhibitor of choline transport, was studied as a prototypic molecular imaging probe in PC-3 cells and 9L glioma-bearing rats. [(3)H]Choline uptake by PC-3 cells was found to have both facilitative and nonfacilitative components. Facilitative transport was characterized by partial sodium dependence and intermediate affinity (K(M) = 9.7 +/- 0.8 microM). HC-3 inhibited choline with a K(I) of 10.5+/- 2.2 microM. Ouabain (1 mM) caused a 94% reduction in choline uptake. At physiologic choline concentration, phosphocholine was the rapid and predominant metabolic fate. The binding of [(3)H]HC-3 to PC-3 cells was rapid and specific (competitively blocked with unlabeled HC-3). Biodistribution of [(3)H]HC-3 in 9L glioma-bearing rats showed the ranking of uptake to be kidney > lung > tumor > liver > skeletal muscle congruent with blood > brain. In comparison with [(14)C]choline, [(3)H]HC-3 showed over twofold higher tumor uptake and favorable uptake ratios of tumor to blood, tumor to muscle, tumor to lung, and tumor to liver. The data demonstrate the quantitative importance of an intermediate-affinity, partially sodium-dependent choline transport system on choline processing in PC-3 cancer cells. The biodistribution properties of [(3)H]HC-3 in tumor-bearing rats encourage the development of molecular imaging probes based on choline transporter binding ligands.
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PMID:Choline transporter as a novel target for molecular imaging of cancer. 1715 Jan 62

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.
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PMID:3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate. 1724 Oct 97

The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11) C-Choline positron emission tomography/computerized tomography (PET/CT). After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 mug/L. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.
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PMID:Metronomic treatment with low-dose trofosfamide leads to a long-term remission in a patient with docetaxel-refractory advanced metastatic prostate cancer. 2039 74

Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.
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PMID:Non-FDG PET in the practice of oncology. 2044 72

The present chapter is focused on the role of positron emission tomography/computed tomography (PET/CT) and [11C]-labelled Choline ([11C]Choline) for the management of prostate cancer patients for radiation therapy planning. Although still a matter of debate, PET/CT with [11C]Choline is not routinely recommended for selecting patients for prostate cancer primary radiation treatment. However, due to its high accuracy in detecting and localizing recurrences when a biochemical failure occurs, [11C]Choline PET/CT may play a role in the re-staging phase to distinguish patients with local versus distant relapse, thus influencing patient management (curative versus palliative therapy). Limited data are currently available on the role of [11C]Choline PET/CT in target volume selection and delineation. According to available literature, [11C]Choline PET/CT is not clinically recommendable to plan target volume both for primary prostate treatment and for local recurrence. Nevertheless, promising data suggested a potential role of [11C]Choline PET/CT as an image guide tool for the irradiation of prostate cancer relapse.
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PMID:Clinical evidence on PET/CT for radiation therapy planning in prostate cancer. 2070 11

Radiotherapy is one of the corner stone treatments for patients with prostate cancer. Especially for locally advanced tumors radiotherapy +/- adjuvant androgen deprivation treatment is standard of care. This brings up the need for accurate assessment of extra prostatic tumor growth and/or the presence of nodal metastases for selection of the optimal radiation dose and treatment volume. Morphological imaging like transrectal ultra sound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used but are limited in their accuracy in detecting extra prostatic extension and nodal metastases. In this article we present a structured review of the literature on positron emission tomography (PET)/CT and radiotherapy in prostate cancer patients with emphasis on: 1) the pretreatment assessment of extra prostatic tumor extension, nodal and distant metastases; 2) the intraprostatic tumor characterization and radiotherapy treatment planning; and 3) treatment evaluation and the use of PET/CT in guidance of salvage treatment. PET/CT is not an appropriate imaging technique for accurate T-staging of prostate cancer prior to radiotherapy. Although macroscopic disease beyond the prostatic capsule and into the periprostatic fat or in seminal vesicle is often accurately detected, the microscopic extension of prostate cancer remains undetected. Choline PET/CT holds a great potential as a single step diagnostic procedure of lymph nodes and skeleton, which could facilitate radiotherapy treatment planning. At present the use of PET/CT for treatment planning in radiotherapy is still experimental. Choline PET based tumor delineation is not yet standardized and different segmentation-algorithms are under study. However, dose escalation using dose-painting is feasible with only limited increases of the doses to the bladder and rectum wall. PET/CT using either acetate or choline is able to detect recurrent prostate cancer after radiotherapy but stratification of patients for any local salvage treatment has not been addressed in the current literature.
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PMID:PET/CT and radiotherapy in prostate cancer. 2092 21


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