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)

Prostate-specific promoters are frequently employed in gene-mediated molecular imaging and therapeutic vectors to diagnose and treat castration-resistant prostate cancer (CRPC) that emerges from hormone ablation therapy. Many of the conventional prostate-specific promoters rely on the androgen axis to drive gene expression. However, considering the cancer heterogeneity and varying androgen receptor status, we herein evaluated the utility of prostate-specific enhancing sequence (PSES), an androgen-independent promoter in CRPC. The PSES is a fused enhancer derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen gene regulatory region. We augmented the activity of PSES by the two-step transcriptional amplification (TSTA) system to drive the expression of imaging reporter genes for either bioluminescent or positron emission tomography (PET) imaging. The engineered PSES-TSTA system exhibits greatly elevated transcriptional activity, androgen independency, and strong prostate specificity, verified in cell culture and preclinical animal experimentations. These advantageous features of PSES-TSTA elicit superior gene expression capability for CRPC in comparison with the androgen-dependent PSA promoter-driven system. In preclinical settings, we showed robust PET imaging capacity of PSES-TSTA in a castrated prostate xenograft model. Moreover, intravenous administrated PSES-TSTA bioluminescent vector correctly identified tibial bone marrow metastases in 9 of 9 animals, whereas NaF- and FDG-PET was unable to detect the lesions. Taken together, this study showed the promising utility of a potent, androgen-independent, and prostate cancer-specific expression system in directing gene-based molecular imaging in CRPC, even in the context of androgen deprivation therapy.
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PMID:Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer. 2193 83

Radiolabeled peptides targeted against receptors on the cell surface have been shown to be remarkably specific and effective in the diagnosis and therapy of malignant disease. Much of the early work in this field took place outside the United States, but in recent years the research effort within the United States has accelerated. Most of the initial studies in the United States focused on somatostatin receptor ligands. (111)In-pentetreotide was approved in 1994 and has been used extensively in the diagnosis and management of a wide variety of neuroendocrine tumors, particularly carcinoid. This work was extended to (99m)Tc-labeled analogs, and the most successful, (99m)Tc-depreotide, was approved in 1999. This agent was found to be accurate in the diagnosis of lung cancer, but it was not particularly successful because it was supplanted by (18)F-FDG imaging with positron tomography. More recently, studies with (68)Ga-labeled somatostatin analogs were initiated in the United States. This effort was delayed relative to that in other parts of the world because of difficulty in obtaining the necessary generators and regulatory uncertainty, both of which are less of a problem currently. Several ligands are being developed to image melanoma through targeting of the melanocyte-stimulating hormone receptor. Other ligands are being developed to use the arginine-glycine-aspartate oligopeptide to target angiogenesis and to use bombesin analogs to target the gastrin-releasing peptide receptor for the diagnosis and potential therapy of prostate cancer. Peptide dimers that target 2 receptors simultaneously are also being constructed, potentially increasing the selectivity of the approach significantly. Radiopeptide therapy has been explored with these ligands, initially with high-dose (111)In-pentetreotide. This step has been followed by U.S. participation in several trials with (90)Y-, (177)Lu-, and (188)Re-labeled analogs. Some of these agents are now available clinically outside the United States, and it is important to design and conduct the appropriate trials so that this therapy can be offered within the United States.
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PMID:Radiopeptide imaging and therapy in the United States. 2242 Sep 83

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 ((11)C) or Fluorine-18 ((18)F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding (11)C-choline or (18)F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to (18)F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and (18)F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to (18)F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.
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PMID:The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review. 2256 40

We present the case of a 74-year-old male with biochemical recurrence of prostate cancer who underwent [(11)C]choline PET/CT. The PET/CT demonstrated an intense focus of uptake within the skull base that was initially felt to potentially represent metastatic disease. Subsequent evaluation with MRI and dedicated thin-section CT revealed this area to be benign fibrous dysplasia of the bone. The focal uptake on PET/CT with [(11)C]choline in benign fibrous dysplasia represents a potential mimicker of metastatic disease. Due to recognizing this benign process, our patient was able to avoid systemic treatment and/or focal radiation and was treated with cryotherapy for biopsy-proven local recurrence within the prostate bed. While benign fibrous dysplasia can demonstrate increased radiotracer uptake on other modalities (i.e., bone scintigraphy, FDG PET/CT), its appearance on [(11)C]choline PET/CT has been largely overlooked in the literature. With the increasing use of [(11)C]choline PET/CT for biochemical recurrent prostate cancer evaluation, it is important to understand this potential mimicker of disease.
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PMID:Benign fibrous dysplasia on [(11)C]choline PET: a potential mimicker of disease in patients with biochemical recurrence of prostate cancer. 2267 39

In this brief review, the major potential clinical applications of 18F-FDG, 11C-acetate, 18F-FDHT, 18F-FLT, 18F-FMAU, and anti-18F-FACBC in the imaging evaluation of men with prostate cancer are discussed. 18F-FDG has a limited role in primary diagnosis and staging but it may be able to reflect tumour aggressiveness, detect sites of recurrence in some men with high serum PSA after biochemical failure and assess response to chemo- and hormonal treatment in metastatic disease. 11C-acetate has been investigated for intra-prostatic primary tumour detection and staging as well as for re-staging in case of biochemical relapse with results that are overall similar to those with 18F- and 11C-labeled choline. 18F-FDHT targets the androgen receptor and may be particularly useful in the assessment of the pharmacodynamics of the androgen signalling pathway. PET in conjunction with 18F-FLT or 18F-FMAU that track the thymidine salvage pathway of DNA synthesis has also been investigated for imaging cellular proliferation in prostate cancer. Initial experience with the radiolabeled synthetic amino acid, anti-18F-FACBC, which displays slow urinary excretion has been encouraging but further studies will be needed to decipher its exact role in the imaging management of men with prostate cancer.
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PMID:PET/CT in prostate cancer: non-choline radiopharmaceuticals. 2301 66

The aim of this review is to evaluate clinical applications of (11)C-acetate positron emission tomography (PET). Acetate is quickly metabolized into acetyl-CoA in human cells. In this form it can either enter into the tricarboxylic acid cycle, thus producing energy, as happens in the myocardium, or participate in cell membrane lipid synthesis, as happens in tumor cells. (11)C-acetate PET was originally employed in cardiology, to study myocardial oxygen metabolism. More recently it has also been used to evaluate myocardial perfusion, as well as in oncology. The first studies of (11)C-acetate focused on its use in prostate cancer. Subsequently, (11)C-acetate was studied in other urological malignancies, as well as renal cell carcinoma and bladder cancer. Well differentiated hepatocellular carcinoma represents an (18)F-fluoro-deoxyglucose ((18)F-FDG) PET pitfall, so many authors have proposed to use (11)C-acetate in addition to (18)F-FDG in studying this tumor. (11)C-acetate PET has also been used in other malignancies, such as brain tumors and lung carcinoma. Some authors reported a few cases in which (11)C-acetate PET incidentally found multiple myeloma or rare tumors, such as thymoma, multicentric angiomyolipoma of the kidney and cerebellopontine angle schwannoma. Lastly, (11)C-acetate PET was also employed in a differential diagnosis case between glioma and encephalitis. The numerous studies on (11)C-acetate have demonstrated that it can be used in cardiology and oncology with no contraindications apart from pregnancy and the necessity of a rapid scan. Despite its limited availability, this tracer can surely be considered to be a promising one, because of its versatility and capacity to even detect non (18)F-FDG-avid neoplasm, such as differentiated lung cancer or hepatocellular carcinoma.
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PMID:The clinical use of PET with (11)C-acetate. 2313 1

The (18)F-choline PET-CT (FCH) has better performance in the assessment of patients with prostate cancer than (18)F-FDG. However, similarly, it is also not a tumor specific radiotracer. We present four (18)F-FCH PET-CT scans in which false positive findings were correctly assessed after evaluation with CT, clinical parameters and/or histological analysis.
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PMID:[Pitfalls with 18F-choline PET/CT in patients with prostate cancer]. 2317 42

Clinical recurrence in the absence of biochemical PSA failure is uncommon and accounts for less than 1%; we report a rare case of solitary lung metastasis in a patient with undetectable PSA level (<0.1 ng/mL) after radical prostatectomy (RP) for prostate cancer (PCa). An asymptomatic 75-year-old man nine years after RP showed a solitary lung mass (about 2 cm) at chest radiography; the 18-FDG-PET/CT confirmed the presence of an isolated mass suspicious for primitive pulmonary cancer. The initial histological specimen after RP showed a mixed acinar and ductal PCa (Gleason score 7, pT3aNO stage, negative surgical margins). A segmental pulmonary resection was performed and definitive specimen demonstrated a single ductal PCa metastasis; after six months from surgery the patient was free from recurrence. In conclusion, in patients with atypical PCa variants imaging studies may be considered in the follow up even in presence of undetectable PSA because they could benefit from early salvage therapy.
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PMID:Solitary lung metastasis after radical prostatectomy in presence of undetectable PSA. 2342 45

Prostate cancer is a major public health problem in developed countries. The remarkable biological and clinical heterogeneity of prostate cancer provides unique opportunities as well as challenges for the diagnostic imaging evaluation of this prevalent disease. The disease is characterized by a natural history that ranges from localized slowly growing hormone-dependent tumor progressing to metastatic hormone-refractory disease. PET is an ideal imaging tool for noninvasive interrogation of the underlying tumor biology. (18)F-FDG is the most common PET radiotracer used for oncological applications based upon elevated glucose metabolism in malignant tissue in comparison to normal tissue. FDG uptake in prostate cancer depends on tumor differentiation with low accumulation in well-differentiated tumors and high uptake in aggressive poorly differentiated tumors. Cumulative current evidence suggests that FDG PET may be useful in detection of disease in a small fraction of patients with biochemical recurrence, in the imaging evaluation of extent and treatment response in metastatic disease and in prediction of patient outcome.
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PMID:Imaging evaluation of prostate cancer with 18F-fluorodeoxyglucose PET/CT: utility and limitations. 2342 34

Prostate cancer (PCa) metabolism appears to be unique in comparison with other types of solid cancers. Normal prostate cells mainly rely on glucose oxidation to provide precursors for the synthesis and secretion of citrate, resulting in an incomplete Krebs cycle and minimal oxidative phosphorylation for energy production. In contrast, during transformation, PCa cells no longer secrete citrate and they reactivate the Krebs cycle as energy source. Moreover, primary PCas do not show increased aerobic glycolysis and therefore they are not efficiently detectable with (18)F-FDG-PET. However, increased de novo lipid synthesis, strictly intertwined with deregulation in classical oncogenes and oncosuppressors, is an early event of the disease. Up-regulation and increased activity of lipogenic enzymes (including fatty acid synthase and choline kinase) occurs throughout PCa carcinogenesis and correlates with worse prognosis and poor survival. Thus, lipid precursors such as acetate and choline have been successfully used as alternative tracers for PET imaging. Lipid synthesis intermediates and FA catabolism also emerged as important players in PCa maintenance. Finally, epidemiologic studies suggested that systemic metabolic disorders including obesity, metabolic syndrome, and diabetes as well as hypercaloric and fat-rich diets might increase the risk of PCa. However, how metabolic disorders contribute to PCa development and whether dietary lipids and de novo lipids synthesized intra-tumor are differentially metabolized still remains unclear. In this review, we examine the switch in lipid metabolism supporting the development and progression of PCa and we discuss how we can exploit its lipogenic nature for therapeutic and diagnostic purposes. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
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PMID:The fat side of prostate cancer. 2356 39


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