Diagnostic performance and safety of NMK36 (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid)-PET/CT in primary prostate cancer: multicenter Phase IIb clinical trial

Jpn J Clin Oncol. 2016 Feb;46(2):152-62. doi: 10.1093/jjco/hyv181. Epub 2016 Jan 4.

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.

Keywords: NMK36; anti-[18F]FACBC; clinical trial; positron emission tomography; prostate cancer.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acids* / administration & dosage
  • Amino Acids* / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Biomarkers, Tumor / blood
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / secondary
  • Carboxylic Acids
  • Contrast Media* / administration & dosage
  • Contrast Media* / adverse effects
  • Cyclobutanes* / administration & dosage
  • Cyclobutanes* / adverse effects
  • Humans
  • Lymph Nodes / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Predictive Value of Tests
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / adverse effects
  • Safety
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed* / methods

Substances

  • Amino Acids
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Carboxylic Acids
  • Contrast Media
  • Cyclobutanes
  • Radiopharmaceuticals
  • fluciclovine F-18
  • Prostate-Specific Antigen