In Vivo Imaging of Intraprostatic-Specific Gene Transcription by PET

Pouliot, Frédéric; Karanikolas, Breanne D.W.; Johnson, Mai; Sato, Makoto; Priceman, Saul J.; Stout, David; Sohn, Joanne J.; Satyamurthy, Nagichettiar; deKernion, Jean B.; Wu, Lily

doi:10.2967/jnumed.110.084582

Cited by 16 publications

(17 citation statements)

References 33 publications

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“…In several studies, investigators have successfully used adenoviral vectors to introduce reporter genes with promoters that were derived from the PSA-PSMA gene regulatory region for PET imaging (59)(60)(61). This method may increase the ability to image prostate cancer micrometastases in the future, although further research is necessary to transfer the findings from these preclinical studies to humans.…”

Section: Reporter Gene Imagingmentioning

confidence: 99%

Molecular Imaging of Prostate Cancer

Wibmer¹,

Burger²,

Sala³

et al. 2016

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Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. F-16b-fluoro5a-dihydrotestosterone, PSA = prostate-specific antigen, PSMA = prostate-specific membrane antigen

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Section: Reporter Gene Imagingmentioning

confidence: 99%

Molecular Imaging of Prostate Cancer

Wibmer¹,

Burger²,

Sala³

et al. 2016

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“…Exploitation of these transcriptional alterations in vivo is among several approaches, which can be used to better treat, prognose, or image prostate cancers (PCa) [ 2 - 4 ]. The prostate provides a unique anatomical location to deliver transcription expression-based nanotechnologies directly into the organ through transrectal ultrasound-guided injections, thereby avoiding systemic biodistribution and poor target delivery [ 5 ]. However, the relatively weak activity of many tumor-specific promoters has limited this approach.…”

Section: Introductionmentioning

confidence: 99%

“…One of these approaches, the two-step transcriptional amplification (TSTA) system, has been successfully adapted for optical and PET-based molecular imaging as well as for gene therapy [ 7 - 10 ]. We recently demonstrated that the amplification provided by the TSTA driven by the prostate specific antigen (PSA) promoter ( PSEBC ) was strong enough to image transcriptional activity in the prostate of large immunocompetent mammals following ultrasound-guided transrectal injection and using a clinical PET imaging apparatus [ 5 ]. Despite the high translational potential of these technologies, their ability to detect primary PCa in vivo remains unchartered territory.…”

Section: Introductionmentioning

confidence: 99%

A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer

et al. 2015

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Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and cloned into type 5 adenovirus. PCA3-3STA activity was highly specific for PCa cells, ranging between 98.7- and 108.0-fold higher than that for benign primary prostate epithelial or non-PCa cells, respectively. In human PCa xenografts, PCA3-3STA displayed robust bioluminescent signals at levels that are sufficient to translate to positron emission tomography (PET)-based reporter imaging. Remarkably, when freshly isolated benign or cancerous prostate biopsies were infected with PCA3-3STA, the optical signal produced from primary PCa biopsies was significantly higher than from benign prostate biopsies (4.4-fold, p < 0.0001). PCA3-3STA therefore represents a PCa-specific expression system with the potential to target, with high accuracy, primary or metastatic PCa epithelial cells for imaging, vaccines, or gene therapy.

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“…Burton, et al demonstrated that AdTSTA-sr39tk, an adenoviral vectors expressing HSV1-sr39TK under the control of the PSE-BC promoter amplified through TSTA, could detect sentinel lymph node metastasis in an orthotopic murine model of prostate cancer (Burton et al, 2008). In addition, Pouliot, et al suggested the potential application of AdTSTA-sr39TK for the detection of prostate cancer in a canine model after intraprostatic administration (Pouliot et al, 2011). …”

Section: Promoters That Regulate Reporter Gene Transcription/exprementioning

confidence: 99%

Cancer imaging: Gene transcription-based imaging and therapeutic systems

Bhang

Pomper

2012

The International Journal of Biochemistry & Cell Biology

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Molecular-genetic imaging of cancer is in its infancy. Over the past decade gene reporter systems have been optimized in preclinical models and some have found their way into the clinic. The search is on to find the best combination of gene delivery vehicle and reporter imaging system that can be translated safely and quickly. The goal is to have a combination that can detect a wide variety of cancers with high sensitivity and specificity in a way that rivals the current clinical standard, positron emission tomography with [18F]fluorodeoxyglucose. To do so will require systemic delivery of reporter genes for the detection of micrometastases, and a nontoxic vector, whether viral or based on nanotechnology, to gain widespread acceptance by the oncology community. Merger of molecular-genetic imaging with gene therapy, a strategy that has been employed in the past, will likely be necessary for such imaging to reach widespread clinical use.

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In Vivo Imaging of Intraprostatic-Specific Gene Transcription by PET

Cited by 16 publications

References 33 publications

Molecular Imaging of Prostate Cancer

Molecular Imaging of Prostate Cancer

A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer

Cancer imaging: Gene transcription-based imaging and therapeutic systems

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