Dataset Information

Biological principles and clinical application of positron emission tomography-tracers in prostate cancer: a review.

ABSTRACT: Prostate carcinoma is the most common malignancy in men and the second cause of death by cancer in the western world. Currently, prostate carcinoma's diagnosis is achieved by transrectal ultrasound-guided biopsy (gold-standard), usually requested after an elevation of prostate specific antigen (PSA) levels or an abnormal digital rectal exam or transrectal ultrasound. Nevertheless, this diagnosis sequence sometimes presents with significant limitations. Therefore, there is a need of a diagnosis modality that improves the tumor detection rates and that offers information for its accurate staging, allowing the treatment's planning and administration. Molecular imaging by the means of positron emission tomography uses radiopharmaceuticals labeled with positron-emitting radioisotopes to detect metabolic changes that might be suggestive of cancer tissue. Recently, this technique has suffered a huge dynamic development, and researchers have been working on novel radiotracers agents to improve accuracy in targeting and detecting prostate tumors. On this review, it is highlighted that the most promising positron emission tomography-tracers that will, in a near future, not only improve diagnostic abilities for prostate carcinoma but also open new possibilities for theranostic approaches to treat this malignancy at a world level.

SUBMITTER: Machado Rocha JM

PROVIDER: S-EPMC6664268 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biological principles and clinical application of positron emission tomography-tracers in prostate cancer: a review.

Machado Rocha José M JM Jorge Pereira Bruno A G BAG

Prostate international 20190111 2

Prostate carcinoma is the most common malignancy in men and the second cause of death by cancer in the western world. Currently, prostate carcinoma's diagnosis is achieved by transrectal ultrasound-guided biopsy (gold-standard), usually requested after an elevation of prostate specific antigen (PSA) levels or an abnormal digital rectal exam or transrectal ultrasound. Nevertheless, this diagnosis sequence sometimes presents with significant limitations. Therefore, there is a need of a diagnosis m ...[more]

PMID: 31384604

Similar Datasets

Project description:ObjectivevMIP-II (viral macrophage inflammatory protein 2)/vCCL2 (viral chemotactic cytokine ligand 2) binds to multiple chemokine receptors, and vMIP-II-based positron emission tomography tracer (64Cu-DOTA-vMIP-II: vMIP-II tracer) accumulates at atherosclerotic lesions in mice. Given that it would be expected to react with multiple chemokine receptors on monocytes and macrophages, we wondered if its accumulation in atherosclerosis lesion-bearing mice might correlate with overall macrophage burden or, alternatively, the pace of monocyte recruitment. Approach and Results: We employed a mouse model of atherosclerosis regression involving adenoassociated virus 8 vector encoding murine Apoe (AAV-mApoE) treatment of Apoe-/- mice where the pace of monocyte recruitment slows before macrophage burden subsequently declines. Accumulation of 64Cu-DOTA-vMIP-II at Apoe-/- plaque sites was strong but declined with AAV-mApoE-induced decline in monocyte recruitment, before macrophage burden reduced. Monocyte depletion indicated that monocytes and macrophages themselves were not the only target of the 64Cu-DOTA-vMIP-II tracer. Using fluorescence-tagged vMIP-II tracer, competitive receptor blocking with CXCR4 antagonists, endothelial-specific Cre-mediated deletion of CXCR4, CXCR4-specific tracer 64Cu-DOTA-FC131, and CXCR4 staining during disease progression and regression, we show endothelial cell expression of CXCR4 is a key target of 64Cu-DOTA-vMIP-II imaging. Expression of CXCR4 was low in nonplaque areas but strongly detected on endothelium of progressing plaques, especially on proliferating endothelium, where vascular permeability was increased and monocyte recruitment was the strongest.ConclusionsEndothelial injury status of plaques is marked by CXCR4 expression and this injury correlates with the tendency of such plaques to recruit monocytes. Furthermore, our findings suggest positron emission tomography tracers that mark CXCR4 can be used translationally to monitor the state of plaque injury and monocyte recruitment.

Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Biological principles and clinical application of positron emission tomography-tracers in prostate cancer: a review.

Publications

Biological principles and clinical application of positron emission tomography-tracers in prostate cancer: a review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure