Molecular imaging of prostate cancer

Boustani, Anne Marie; Pucar, Darko; Saperstein, Lawrence

doi:10.1259/bjr.20170736

Cited by 20 publications

(13 citation statements)

References 62 publications

(72 reference statements)

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“…These imaging modalities consist of a radionuclide conjugated to a receptor-targeting agent or metabolic compound. The most widely-studied molecular imaging targets in prostate cancer include prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in prostate cancer cells, and dihydrotestosterone (DHT), the primary ligand for the AR ( 95 ). While PSMA and DHT are relatively specific for prostate cancer, compounds such as fluoro-2-D-deoxyglucose (FDG), choline, acetate, and fluciclovine more broadly detect metabolic activity.…”

Section: Novel Biomarkersmentioning

confidence: 99%

Clinical considerations for the management of androgen indifferent prostate cancer

Berchuck

Viscuse

Beltran

et al. 2021

Prostate Cancer Prostatic Dis

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Background: Many systemic therapies for advanced prostate cancer work by disrupting androgen receptor signaling. Androgen indifferent prostate cancer (AIPC) variants, including aggressive variant prostate cancer (AVPC), neuroendocrine prostate cancer (NEPC), and double negative prostate cancer (DNPC), are increasingly common and often overlapping resistance phenotypes following treatment with androgen receptor signaling inhibitors in men with metastatic castration-resistant prostate cancer and are associated with poor outcomes. Understanding the underlying biology and identifying effective therapies for AIPC is paramount for improving survival for men with prostate cancer. Methods: In this review, we summarize the current knowledge on AIPC variants, including our current understanding of the clinical, morphologic, and molecular features as well as current therapeutic approaches. We also explore emerging therapies and biomarkers aimed at improving outcomes for men with AIPC. Results and Conclusions: Establishing consensus definitions, developing novel biomarkers for early and accurate detection, further characterization of molecular drivers of each phenotype, and developing effective therapies will be critical to improving outcomes for men with AIPC. Significant progress has been made towards defining the clinical and molecular characteristics of AVPC, NEPC, and DNPC. Novel diagnostic approaches, including cell-free DNA, circulating tumor cells, and molecular imaging are promising tools for detecting AIPC in clinical practice. Building on previous treatment advances, several clinical trials are underway evaluating novel therapeutic approaches in patients with AIPC informed by an understanding of variant-specific biology. In this review, we discuss how these recent and ongoing studies will help to improve diagnosis, prognosis, and therapy for men with AIPC.

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Section: Novel Biomarkersmentioning

confidence: 99%

Clinical considerations for the management of androgen indifferent prostate cancer

Berchuck

Viscuse

Beltran

et al. 2021

Prostate Cancer Prostatic Dis

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“…PSMA inhibitors are most commonly coupled with Ga-68 or F-18 and used for PET/computerized tomography (CT) and PET/MRI. 25 The ability to ascertain the presence and extent of metastatic prostate cancer has been significantly increased through the introduction of imaging agents targeting PSMA, which provide superior diagnostic performance compared with alternative techniques, with a calculated positive predictive value of >95%. 26 While the research developing positron emitter-based imaging agents targeting PSMA is vigorous, the development of Tc-99m-based imaging agents is still important when the high incidence of prostate cancer and increasing global demand for Tc-99m are considered.…”

Section: Discussionmentioning

confidence: 99%

Dual‐labeled prostate‐specific membrane antigen (PSMA)‐targeting agent for preoperative molecular imaging and fluorescence‐guided surgery for prostate cancer

Kim

2020

Labelled Comp Radiopharmac

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The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc‐99m GRFLTGGTGRLLRIS‐GHEG‐ECG‐K(‐5‐carboxy‐X‐rhodamine)‐NH2 (GRFLT‐ECG‐ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT‐ECG‐ROX was synthesized using Fmoc solid‐phase peptide synthesis. Radiolabeling of GRFLT‐ECG‐ROX with Tc‐99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC‐3 tumor‐bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc‐99m, Tc‐99m GRFLT‐ECG‐ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd) of Tc‐99m GRFLT‐ECG‐ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc‐99m GRFLT‐ECG‐ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real‐time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc‐99m GRFLT‐ECG‐ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.

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“…Cells were categorized as CTCs based on the clinically valid definition of CTC, which is a nucleated cell larger than 4 μm that expresses epithelial proteins, such as cytokeratins 8, 18, and/or 19, while being negative for the leukocyte-specific antigen CD-45 46 . Moreover, we have incorporated the expression of the prostate specific membrane antigen (PSMA) as a parameter to categorize cells as CTCs; PSMA is a transmembrane protein that is usually overexpressed in nearly all malignant prostate cancer cells and its expression increases as the disease progresses 47,48 . The categorization of CTCs based on PSMA expression is sustained by studies that report the successful isolation of CTCs from blood samples of prostate cancer patients using antibodies against PSMA as the capture strategy 21,49,50 .…”

Section: Detection Of Ctcs From Samples Of Patients With Metastatic Pmentioning

confidence: 99%

Characterization of a novel automated microfiltration device for the efficient isolation and analysis of circulating tumor cells from clinical blood samples

León¹,

Soto-García²,

Araíz-Hernández³

et al. 2020

Sci Rep

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The detection and analysis of circulating tumor cells (CTCs) may enable a broad range of cancer-related applications, including the identification of acquired drug resistance during treatments. However, the non-scalable fabrication, prolonged sample processing times, and the lack of automation, associated with most of the technologies developed to isolate these rare cells, have impeded their transition into the clinical practice. This work describes a novel membrane-based microfiltration device comprised of a fully automated sample processing unit and a machine-vision-enabled imaging system that allows the efficient isolation and rapid analysis of CTCs from blood. The device performance was characterized using four prostate cancer cell lines, including PC-3, VCaP, DU-145, and LNCaP, obtaining high assay reproducibility and capture efficiencies greater than 93% after processing 7.5 mL blood samples spiked with 100 cancer cells. Cancer cells remained viable after filtration due to the minimal shear stress exerted over cells during the procedure, while the identification of cancer cells by immunostaining was not affected by the number of non-specific events captured on the membrane. We were also able to identify the androgen receptor (AR) point mutation T878A from 7.5 mL blood samples spiked with 50 LNCaP cells using RT-PCR and Sanger sequencing. Finally, CTCs were detected in 8 out of 8 samples from patients diagnosed with metastatic prostate cancer (mean ± SEM = 21 ± 2.957 CTCs/mL, median = 21 CTCs/mL), demonstrating the potential clinical utility of this device. In the last two decades, circulating tumor cells (CTCs) have attracted a significant amount of attention for their potential use as a blood-based biomarker for a broad range of cancer-related clinical applications. CTCs are malignant cells that are shed from the primary and/or metastatic solid tumors and then infiltrate into the vascular and lymphatic systems; these cells play a fundamental role in the metastatic process of non-hematological cancers 1-3. Although the first report describing the existence of CTCs dates from 1869 4 , the heterogeneity and the

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Molecular imaging of prostate cancer

Cited by 20 publications

References 62 publications

Clinical considerations for the management of androgen indifferent prostate cancer

Clinical considerations for the management of androgen indifferent prostate cancer

Dual‐labeled prostate‐specific membrane antigen (PSMA)‐targeting agent for preoperative molecular imaging and fluorescence‐guided surgery for prostate cancer

Characterization of a novel automated microfiltration device for the efficient isolation and analysis of circulating tumor cells from clinical blood samples

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