Prostate cancer affects 1 in 6 men and is the second leading cause of cancer death. Definitive diagnosis is based on systematic transrectal ultrasound (TRUS)-guided prostate biopsy typically prompted by the widespread use of prostate specific antigen (PSA) screening. However, this procedure misses about 40% of prostate cancers leading to repeat biopsies at significant patient morbidity and healthcare cost. Therefore, there is an unmet critical need for image-guided biopsy that maximizes the probability of detection of clinically relevant tumors in order to circumvent the current underdiagnsois (and undertreatment) of lethal tumors and conversely overdiagnosis (and overtreatment) of indolent tumors. Image-guided prostate tumor detection and characterization will pave the way for rational treatment management strategy including the emerging focal therapy for organ-confined high grade tumors. Multiparametric magnetic resonance imaging (mpMRI) has been reported to offer relatively high specificity but variable sensitivity for prostat cancer detection. The potential use of positron emission tomography (PET) with a variety of tracers has primarily focused on the biochemical recurrence and the castrate-resistant metastatic phases of the disease. There is currently paucity of data for any PET tracer relevant to the accurate detection, localization, and characterization of primary tumor in patients with suspected prostate cancer, particularly after an initial negative standard TRUS guided biopsy. We have had a long record of interest and experience with the synthesis and evaluation of the cellular proliferation and cellular stress biomarker, 18F-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) in conjunction with PET. Our efforts have included completion of an R21-funded preclinical evaluation of 18F-FMAU in animal models of prostate cancer, and since the prior review, attainment of sufficient funds for an IRB-RDRC approved proof-of-concept clinical case study in one patient, and recent submission of an Investigational New Drug application to the US Food and Drug Administration. We are now in a strategic position to continue along this line of research with additional pilot human-based feasibility tria. Therefore, the objective of this revised R21 proposal is to perform a systematic study of 18F-FMAU in men with suspected primary prostate cancer for detection, localization and characterization of primary tumor at the time of initial diagnosis. The two specific aims of this proposal are: 1) to perform a prospective clinical imaging evaluation of 18F-FMAU PET/CT for detection and localization of primary tumor in 40 men with suspected prostate cancer based on elevated/rising prostate specific antigen level including those with prior negative biopsy who are scheduled to undergo clinical mpMRI and TRUS-guided biopsy procedure, and 2) to examine the associations between the PET and mpMRI derived imaging parameters and the biopsy histopathology parameters as well as serum prostate specific antigen level and kinetics. The underlying hypothesis is that 18F-FMAU accumulates in primary prostate cancer allowing for image-directed biopsy with an uptake level that is reflective of tumor proliferation index. We believe that addition of 18F-FMAU PET/CT in conjunction with mpMRI directed prostate biopsy will markedly improve the current status quo and impact the diagnostic evaluation of men with suspected prostate cancer.

Public Health Relevance

The goal of our project is to use image-directed biopsy for personalized management of men with suspected prostate cancer. Based on encouraging results of our preclinical and one clinical case evaluation of the cellular proliferation biomarker 18F-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) in conjunction with PET/CT, we now propose to perform a pilot clinical trial in men with suspected prostate cancer. We expect that addition of 18F-FMAU PET/CT directed prostate biopsy to multiparametric MRI and standard TRUS- guided biopsy procedure impacts the clinical management considerably by improving localization and characterization (indolent vs. lethal) of prostate tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB017568-01A1
Application #
9036232
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Sastre, Antonio
Project Start
2015-09-04
Project End
2017-06-30
Budget Start
2015-09-04
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
$237,100
Indirect Cost
$87,100
Name
University of Southern California
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Jadvar, Hossein; Chen, Xiaoyuan; Cai, Weibo et al. (2018) Radiotheranostics in Cancer Diagnosis and Management. Radiology 286:388-400
Chau, Albert; Gardiner, Peter; Colletti, Patrick M et al. (2018) Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases. Clin Nucl Med 43:e226-e231
Varghese, Bino; Velez, Erik; Desai, Bhushan et al. (2018) Incidental Detection of Meningioma by 18F-FMAU PET/CT in a Patient With Suspected Prostate Cancer. Clin Nucl Med 43:e245-e246
Jadvar, Hossein (2017) Highlights of articles published in annals of nuclear medicine 2016. Eur J Nucl Med Mol Imaging 44:1928-1933
Jadvar, Hossein; Park, Ryan; Yap, Li-Peng et al. (2017) Effect of Androgen on Normal Biodistribution of [18F]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) in Athymic Non-tumor-bearing Male Mice. Anticancer Res 37:475-479
Jadvar, Hossein (2017) Multimodal Imaging in Focal Therapy Planning and Assessment in Primary Prostate Cancer. Clin Transl Imaging 5:199-208
Jadvar, Hossein (2017) Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment. AJR Am J Roentgenol 209:277-288
Jadvar, Hossein (2016) PET of Glucose Metabolism and Cellular Proliferation in Prostate Cancer. J Nucl Med 57:25S-29S
Zukotynski, Katherine; Jadvar, Hossein; Capala, Jacek et al. (2016) Targeted Radionuclide Therapy: Practical Applications and Future Prospects. Biomark Cancer 8:35-8
Kitajima, Kazuhiro; Yamamoto, Shingo; Fukushima, Kazuhito et al. (2016) Update on advances in molecular PET in urological oncology. Jpn J Radiol 34:470-85

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