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 contrastenhanced 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.

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs

“…In a report of a multicenter phase 2b clinical trial for the staging of primary prostate cancer, 68 patients with a mean PSA level of 88.6 ng/mL underwent both whole-body 18 F-fluciclovine PET/CT and conventional imaging with CT and bone scanning (48). Overall similar accuracies-85.5% and 87.3%-were reported for 18 Ffluciclovine PET/CT and conventional imaging, respectively.…”

Update on 18F-Fluciclovine PET for Prostate Cancer Imaging

“…(32). In a study involving 68 patients, 18F-fluciclovine PET-CT was found to have a moderate concordance rate of osseous metastatic disease when compared to combined bone scintigraphy and contrast enhanced CT; however, 7 patients did have positive 18F-fluciclovine findings which were negative on combined conventional bone scan and contrast enhanced CT imaging (16). While it may be concluded that a dedicated bone scan may not be necessary if a patient has definitively positive osseous disease with 18F-fluciclovine PET, most early clinical trials utilized a positive bone scan as an exclusion criteria.…”

“…For personal use only. jnm.snmjournals.org Downloaded from whole body contrast enhanced CT, and found a sensitivity, specificity and accuracy of 64.5%, 99.6%, and 95.5% for extraprostatic nodal disease with 18F-fluciclovine PET-CT vs 71%, 100%, and 96.6% for contrast enhanced CT for nodal disease > 1 cm in the short axis (16). Though unable to be confirmed with the reference standard, 18F-fluciclovine PET detected subcentimeter (5-9 mm) lymph nodes in 13 patients not considered positive by CT. A recent study of 28 patients with high risk prostate cancer underwent simultaneous 18F-fluciclovine PET-MRI prior to surgery and found a high specificity (100%) but low sensitivity (30%) for detection of regional lymph node metastases (21).…”

“…Additionally, it should be noted that primary tumor characterization is not an FDA approved indication. A multicenter trial involving 68 patients with primary prostate cancer and who were scheduled for either radical prostatectomy or hormone therapy, underwent 18F-fluciclovine PET-CT imaging and found a high sensitivity and specificity of 92.5% and 90.1% for the focus of primary disease (16). Yet, additional studies reported lower specificity in the prostate.…”

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

“…Recently, phase II clinical trials of [ 18 F]fluciclovine have been simultaneously conducted in Japan for the diagnosis of glioma [2] and primary prostate cancer [3]. …”