Evaluation of Castration-Resistant Prostate Cancer with Androgen Receptor–Axis Imaging

Pandit‐Taskar, Neeta; Veach, Darren R.; Fox, Josef J.; Scher, Howard I.; Morris, Michael J.; Larson, Steven M.

doi:10.2967/jnumed.115.170134

Cited by 16 publications

(14 citation statements)

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“…Plausible explanations may include: (1) incomplete chemical castration and AR blockage; (2) intracrine androgen production; (3) and inter-dependent symbiotic relationship between AR +/hi and AR −/lo cells. On the other hand, it is conceivable that in mCRPC patients, some metastatic foci may be predominantly AR +/hi while others primarily AR −/lo (reviewed in 2), as reported recently in patient metastases 32 , 33 , 35 .…”

Section: Discussionmentioning

confidence: 85%

“…8k ). PCa metastases, which are generally clonal in origin, may manifest as either AR + or AR −/lo , as evidenced by commonly used, mostly metastasis-derived PCa cell lines (e.g., PC3, DU145, and PPC-1 being AR - whereas LNCaP, LAPC9, VCaP, LAPC4 being AR + ), as well as by recent positron emission tomography/computed tomography-based AR-axis imaging analysis 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

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Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses

et al. 2018

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Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity remains unclear. Screening ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89 patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR−/lo). Xenograft modeling demonstrates that AR+ CRPC is enzalutamide-sensitive but AR−/lo CRPC is resistant. Genome editing-derived AR+ and AR-knockout LNCaP cell clones exhibit distinct biological and tumorigenic properties and contrasting responses to enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental combinatorial therapy, identify BCL-2 as a critical therapeutic target and provide proof-of-concept therapeutic regimens for both AR+/hi and AR−/lo CRPC. Our study links AR expression heterogeneity to distinct castration/enzalutamide responses and has important implications in understanding the cellular basis of prostate tumor responses to AR-targeting therapies and in facilitating development of novel therapeutics to target AR−/lo PCa cells/clones.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses

et al. 2018

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“…AR-targeted imaging with 18 F-FDHT is an interesting area of current research for pretreatment stratification and therapeutic response assessment in castration-resistant patients evaluated for newer, high-affinity AR inhibitor therapy (e.g., enzalutamide) (75). In combination with 18 F-FDG, 18 F-FDHT PET/CT may also be a useful marker of PCa heterogeneity.…”

Section: Imaging Mcrpcmentioning

confidence: 99%

Multimodality Imaging of Prostate Cancer

2019

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) the various distinct clinical scenarios for prostate cancer; (2) the various imaging modalities available for use in prostate cancer; (3) the role of these imaging modalities in primary or recurrent prostate cancer and their advantages and disadvantages; and (4) the future potential of theranostic approaches and the evolving indications for contemporary hybrid imaging modalities such as PET/MRI and whole-body MRI. Financial Disclosure: Dr. Burger has received research grants and speaker honorarium from GE Healthcare. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through October 2022. Prostate cancer is a very heterogeneous disease, and contemporary management is focused on identification and treatment of the prognostically adverse high-risk tumors while minimizing overtreatment of indolent, low-risk tumors. In recent years, imaging has gained increasing importance in the detection, staging, posttreatment assessment, and detection of recurrence of prostate cancer. Several imaging modalities including conventional and functional methods are used in different clinical scenarios with their very own advantages and limitations. This continuing medical education article provides an overview of available imaging modalities currently in use for prostate cancer followed by a more specific section on the value of these different imaging modalities in distinct clinical scenarios, ranging from initial diagnosis to advanced, metastatic castration-resistant prostate cancer. In addition to established imaging indications, we will highlight some potential future applications of contemporary imaging modalities in prostate cancer.

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“…The 4-author team of investigators from Germany, Japan, and Stanford present the next paper, which is on the potential clinical utility of radiotracers targeted to the gastrin-releasing peptide receptors (12). Then, the group from Memorial Sloan Kettering Cancer Center, led by Steven Larson, discusses the development and evaluation of androgen receptor axis-based radiotracers in the biologic context of castration-resistant metastatic prostate cancer (13). The next 3 articles focus on the exciting results from theranostics based on prostate-specific membrane antigen (PSMA) as the biomarker.…”

Section: Thi S Special Supplemental Issue Of the Journal Of Nuclearmentioning

confidence: 99%

Radiotheranostics in Prostate Cancer: Introduction and Overview

Jadvar

2016

J Nucl Med

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Evaluation of Castration-Resistant Prostate Cancer with Androgen Receptor–Axis Imaging

Cited by 16 publications

References 46 publications

Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses

Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses

Multimodality Imaging of Prostate Cancer

Radiotheranostics in Prostate Cancer: Introduction and Overview

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