title: Diagnostic performance and safety of NMK36 (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid)-PET/CT in primary prostate cancer: multicenter Phase IIb clinical trial.
abstract: OBJECTIVE
  We performed a multicenter Phase IIb clinical trial of NMK36, a novel amino acid analog for positron emission tomography containing trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid, to evaluate its safety and diagnostic performance for primary prostate cancer.
  
  
  METHODS
  Sixty-eight subjects with primary prostate cancer scheduled for radical prostatectomy or hormone therapy underwent whole-body positron emission tomography/computed tomography after injection of NMK36. The diagnostic performances of NMK36-positron emission tomography/computed tomography were evaluated for (i) regional lymph node metastasis: comparison with contrast-enhanced computed tomography under setting reference standard (histopathology or 6-month follow-up), (ii) bone metastasis: concordance rate with conventional imaging (combination of bone scintigraphy and contrast-enhanced computed tomography) and (iii) primary lesion: comparison with histopathological findings.
  
  
  RESULTS
  The accuracy of NMK36-positron emission tomography/computed tomography and contrast-enhanced computed tomography for regional lymph node metastasis were 85.5 and 87.3%, respectively. NMK36-positron emission tomography/computed tomography showed positive findings for regional lymph nodes with short-axis diameters of 5-9 mm at 23 regions in 13 patients of hormone therapy cohort, but they were not confirmed with reference standard in this study. The concordance rate of NMK36-positron emission tomography/computed tomography with conventional imaging for bone metastases was 83.3%, and seven patients had positive findings only by NMK36-positron emission tomography/computed tomography. The sensitivity and specificity of NMK36-positron emission tomography/computed tomography for primary lesion in six-segment analysis was 92.5 and 90.1%, respectively. Seven of non-serious adverse events were observed in six patients.
  
  
  CONCLUSIONS
  This study showed the comparable diagnostic performance of NMK36-positron emission tomography/computed tomography compared with conventional imaging. Some lesions of lymph node and bone were positive solely by NMK36-positron emission tomography/computed tomography, which needs to be confirmed with reference standard in future study to evaluate the usefulness of NMK36-positron emission tomography/computed tomography in staging prostate cancer.
authors.affiliation: Department of Urology, Toho University Sakura Medical Center, Sakura hiroyoshi.suzuki@med.toho-u.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Diagnostic Radiology, Kitasato University School of Medicine, Sagamihara.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Urology, National Cancer Center Hospital, Tokyo.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujimoto
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Prostate Center and Division of Urology, Chiba Cancer Center, Chiba.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukasawa
authors.affiliation: Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama.
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, National Hospital Organization Tokyo Medical Center, Tokyo.
authors.forename: Shiro
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Clinical Development Department, Nihon Medi-Physics Co., Ltd., Tokyo, Japan.
authors.forename: Akiharu
authors.initials: A
authors.lastname: Otaka
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000175:diagnosis / Q000556:secondary; D002264:Carboxylic Acids; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects; D003503:Cyclobutanes / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008198:Lymph Nodes / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects; D012449:Safety; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000596:Amino Acids; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D002264:Carboxylic Acids; D003287:Contrast Media; D003503:Cyclobutanes; D019275:Radiopharmaceuticals; C117460:fluciclovine F-18; D017430:Prostate-Specific Antigen
keywords: NMK36; anti-[18F]FACBC; clinical trial; positron emission tomography; prostate cancer