PSMA-Targeted PET Radiotracer [¹⁸F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease

Mohamed Saleh Ismail1 Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Diane E Peters2 Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA;3 Johns Hopkins Drug Discovery, Baltimore, MD, USA

Steven P Rowe4 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA;5 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Ali Salavati6 Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA

Sowmya Sharma1 Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

https://orcid.org/0000-0002-3803-1537

Robert A Anders7 The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Martin Pomper2 Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA;4 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA;5 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

https://orcid.org/0000-0001-6753-3010

Barbara S Slusher2 Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA;3 Johns Hopkins Drug Discovery, Baltimore, MD, USA;8 Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Florin M Selaru1 Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;5 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USACorrespondence[email protected] [email protected]

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Abstract

Background

Prostate-specific membrane antigen (PSMA) is highly and specifically upregulated in active-inflamed mucosa of patients with inflammatory bowel disease (IBD). We hypothesized that this upregulation would be detectable using a PSMA-targeted positron emission tomography/computed tomography (PET/CT) imaging agent, [¹⁸F]DCFPyL, enabling non-invasive visualization of inflammation. A noninvasive means of detecting active inflammation would have high clinical value in localization and management of IBD.

Study

We performed [¹⁸F]DCFPyL imaging in three IBD patients with active disease. Abnormally increased gastrointestinal [¹⁸F]DCFPyL uptake was observed in areas with endoscopic, histologic, and immunohistochemical inflammation, demonstrating partial overlap of segments of bowel with abnormal [¹⁸F]DCFPyL uptake and active inflammation.

Conclusion

This study demonstrates that PSMA-targeted [¹⁸F]DCFPyL PET can effectively detect regions of inflamed mucosa in patients with IBD, suggesting its utility as a non-invasive imaging agent to assess location, extent, and disease activity in IBD.

Keywords:

Disclosure

M.P. is a coinventor on a US patent covering [¹⁸F]DCFPyL and as such is entitled to a portion of any licensing fees and royalties generated by this technology. B.S.S. and D.E.P. are coinventors on Johns Hopkins patent applications covering the use and novel compositions of PSMA inhibitors as IBD therapeutics. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. D.E.P. also reports NIH T32 training grant (T32 OD011089). S.P.R. is a consultant to Progenics Pharmaceuticals, the licensee of [¹⁸F]DCFPyL. S.P.R. and M.P. receive research funding from Progenics Pharmaceuticals. M.P. is a founder of Precision Molecular, Inc. S.P.R. and M.P. are consultants to Precision Molecular, Inc. The authors report no other conflicts of interest in this work.

PSMA-Targeted PET Radiotracer [¹⁸F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease

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PSMA-Targeted PET Radiotracer [18F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease

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PSMA-Targeted PET Radiotracer [¹⁸F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease