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Fluorine-18 Prostate-specific Membrane Antigen-1007 Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Diagnostics of Local Recurrence in a Prostate Cancer Patient After Recent Radical Prostatectomy

Open AccessPublished:October 05, 2017DOI:https://doi.org/10.1016/j.clgc.2017.09.014

      Keywords

      Clinical Practice Points
      • We performed fluorine-18 (18F) prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/computed tomography (CT) in 1 patient with biochemical recurrence (prostate-specific antigen level, 0.3 ng/mL) after radical prostatectomy.
      • Diagnostic certainty using multiparametric magnetic resonance imaging was significantly reduced compared with PET in this case for the detection of local prostate cancer recurrence.
      • 18F-PSMA-1007 PET/CT scanning revealed focal intense PSMA uptake in the former right prostatic bed, indicating local recurrence.

      Introduction

      In recent years, prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), mostly bound to gallium-68 (68Ga), has significantly emerged as the diagnostic tool of choice for primary prostate cancer staging and as an imaging modality for biochemical recurrence.
      • Rauscher I.
      • Maurer T.
      • Beer A.J.
      • et al.
      Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: comparison with histopathology after salvage lymphadenectomy.
      • Eiber M.
      • Maurer T.
      • Souvatzoglou M.
      • et al.
      Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy.
      • Afshar-Oromieh A.
      • Malcher A.
      • Eder M.
      • et al.
      PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions.
      • Perera M.
      • Papa N.
      • Christidis D.
      • et al.
      Sensitivity, specificity, and predictors of positive 68Ga–prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis.
      However, according to recent guidelines, multiparametric magnetic resonance imaging MRI (mpMRI) should be the modality of choice for initial local staging and for assessment of local recurrence.
      • Heidenreich A.
      • Bastian P.J.
      • Bellmunt J.
      • et al.
      EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013.
      • Heidenreich A.
      • Bastian P.J.
      • Bellmunt J.
      • et al.
      EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer.
      • Morlacco A.
      • Sharma V.
      • Viers B.R.
      • et al.
      The incremental role of magnetic resonance imaging for prostate cancer staging before radical prostatectomy.
      In addition, although serving as a comparable diagnostic tool for primary staging and as a favorable imaging modality for local recurrence, 68Ga-PSMA PET/CT has the disadvantage of bladder activity, which can be a problem for local recurrence detection.
      • Eiber M.
      • Weirich G.
      • Holzapfel K.
      • et al.
      Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the localization of primary prostate cancer.
      • Maurer T.
      • Gschwend J.E.
      • Rauscher I.
      • et al.
      Diagnostic efficacy of (68)gallium-PSMA-PET compared to conventional imaging in lymph node staging of of 130 consecutive patients with intermediate to high-risk prostate cancer.
      • Freitag M.T.
      • Radtke J.P.
      • Hadaschik B.A.
      • et al.
      Comparison of hybrid 68Ga-PSMA PET/MRI and 68Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer.
      The novel PET tracer fluorine-18 [18F]-PSMA-1007 has some advantageous characteristics that make it a promising candidate to compete with 68Ga-PSMA PET/CT.
      • Giesel F.L.
      • Hadaschik B.
      • Cardinale J.
      • et al.
      F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.

      Kesch C, Vinsensia M, Radtke JP, et al. Intra-individual comparison of 18 F-PSMA-1007-PET/CT, multi-parametric MRI and radical prostatectomy specimen in patients with primary prostate cancer—a retrospective, proof of concept study [e-pub ahead of print]. J Nucl Med 2017, https://doi.org/10.2967/jnumed.116.189233.

      With PET radiopharmacies connected to an on-site cyclotron, 18F-PSMA-1007 can be produced on a large scale.

      Kesch C, Vinsensia M, Radtke JP, et al. Intra-individual comparison of 18 F-PSMA-1007-PET/CT, multi-parametric MRI and radical prostatectomy specimen in patients with primary prostate cancer—a retrospective, proof of concept study [e-pub ahead of print]. J Nucl Med 2017, https://doi.org/10.2967/jnumed.116.189233.

      Additionally, 18F-PSMA-1007 is primarily eliminated by hepatobiliary excretion owing to its moderate lipophilic characteristics.
      • Giesel F.L.
      • Hadaschik B.
      • Cardinale J.
      • et al.
      F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.
      Therefore, almost no bladder activity occurs, providing ideal conditions for evaluation of the prostate bed.
      • Giesel F.L.
      • Hadaschik B.
      • Cardinale J.
      • et al.
      F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.
      In the present case report, we evaluated the advantages of PSMA PET/CT to evaluate a patient with biochemical recurrence and unclear findings on mpMRI.

      Case Report

      In January 2017, prostate cancer (PCa) was diagnosed in a 48-year-old patient. The PCa was Gleason score 3+4 and International Society of Urological Pathology grade 2. The patient underwent radical prostatectomy. The radical prostatectomy specimen revealed pathologic stage T2cN0. The clinical M stage was M0. No adjuvant radiotherapy was administered. The prostate-specific antigen (PSA) level decreased from 7.8 ng/mL preoperatively to 0.1 ng/mL after surgery, indicating biochemical recurrence. Six months later, the patient was referred to our clinic, with a request for imaging using mpMRI owing to an elevated PSA level of 0.3 ng/mL. MRI did not detect any distinct suspicious local tumor growth or lymph node metastases (Figure 1). mpMRI was conducted as described previously using state-of-the-art high b values (b = 0, 1000, and 1500 s/mm2) and T1-weighted dynamic contrast enhancement with 50 time measurements. A smaller contrast-enhanced nodule close to the bladder (Denonvillier fascia) on the right side was noted. However, the certainty of the board-certified radiologist was low, and the finding was reported as unclear. The apparent diffusion coefficient was moderately decreased. The case was reviewed again, and 2 board-certified radiologists confirmed that the very small contrast-enhancing nodule could be mistaken as postoperative scarring.
      Figure thumbnail gr1
      Figure 1Multiparametric Magnetic Resonance Imaging Examination of a 48-Year-old Patient 6 Months After Radical Prostatectomy (Gleason Score 7, Stage pT2cN0M0), When the Patient Presented With an Increasing Prostate-specific Antigen Value of 0.3 ng/mL. (A) T2-weighted Images, (B) T1-weighted Images After Dynamic Contrast Enhancement, and (C) Diffusion-weighted Images With Apparent Diffusion Coefficient Map Did Not Reveal Any Recurrence, Including in the Former Prostatic Bed
      For further investigation, the patient underwent PET/CT with the 18F-labeled PSMA-targeted radiotracer ([18F]PSMA-1007). PET/CT detected focal PSMA ligand uptake in the former right prostatic bed with a maximum standardized uptake value (SUVmax) of 4.95, indicating clear local PCa recurrence (Figure 2). No metastatic lymph nodes or distant metastases were detected on the PSMA PET/CT scan. Therefore, local stereotactic radiotherapy was initiated, with a PSA decrease confirmed during the treatment.
      Figure thumbnail gr2
      Figure 2Fluorine-18 Prostate-specific Membrane Antigen (PSMA)-1007 Positron Emission Tomography (PET)/Computed Tomography (CT) Examination of a 48-Year-old Patient 6 Months After Radical Prostatectomy (Gleason Score 7, Stage pT2cN0M0), When the Patient Presented With an Increasing Prostate-specific Antigen Value of 0.3 ng/mL. (A, B) PET and (C, D) Fused PET/CT Images Showed Intense, Focal PSMA Ligand Uptake (Red Arrow) in the Former Right Prostatic Bed With Maximum Standardized Uptake Value of 4.95, Indicating Local Recurrence

      Discussion

      Up to 40% of patients undergoing radical prostatectomy for primary treatment of PCa will develop biochemical recurrence.
      • Han M.
      • Partin A.W.
      • Pound C.R.
      • Epstein J.I.
      • Walsh P.C.
      Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy.
      • Simmons M.N.
      • Stephenson A.J.
      • Klein E.A.
      Natural history of biochemical recurrence after radical prostatectomy: risk assessment for secondary therapy.
      • Suardi N.
      • Porter C.R.
      • Reuther A.M.
      • et al.
      A nomogram predicting long-term biochemical recurrence after radical prostatectomy.
      • Roehl K.A.
      • Han M.
      • Ramos C.G.
      • Antenor J.A.
      • Catalona W.J.
      Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results.
      • Abdollah F.
      • Briganti A.
      • Montorsi F.
      • et al.
      Contemporary role of salvage lymphadenectomy in patients with recurrence following radical prostatectomy.
      For these patients, precise localization of recurrent disease and accurate restaging is crucial for adequate treatment selection. However, conventional imaging modalities such as CT or MRI have some limitations in the detection of local disease.
      • Hovels A.M.
      • Heesakkers R.A.
      • Adang E.M.
      • et al.
      The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis.
      The role of PET/CT has gradually increased in importance for prostate cancer patients with biochemical relapse. 18F-choline and 11C-choline as markers of membrane cell proliferation are radiotracers currently widely used in clinical practice. However, some studies have reported low sensitivity and specificity, especially in patients with low PSA values.
      • Krause B.J.
      • Souvatzoglou M.
      • Tuncel M.
      • et al.
      The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.
      PSMA ligands have been reported to have greater sensitivity and specificity than the choline derivate.
      • Afshar-Oromieh A.
      • Zechmann C.M.
      • Malcher A.
      • et al.
      Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer.
      Nevertheless, the most significant advantage of 68Ga-PSMA-11 PET/CT is the sensitive detection of lesions even at low PSA levels, even small lymph node metastases, and bone and visceral metastases owing to the low background signal.
      • Perera M.
      • Papa N.
      • Christidis D.
      • et al.
      Sensitivity, specificity, and predictors of positive 68Ga–prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis.
      • Afshar-Oromieh A.
      • Zechmann C.M.
      • Malcher A.
      • et al.
      Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer.
      Also, 68Ga-PSMA-11 ligands have the disadvantage in the assessment of small local recurrences of excretion by way of the kidneys and high accumulation in the urinary bladder.10 18F-PSMA-1007 is an attractive alternative to the Ga-PSMA radioligand, because it has demonstrated better energy and fast, nonurinary background clearance, which greatly improves evaluation of the former left prostatic bed.
      • Giesel F.L.
      • Hadaschik B.
      • Cardinale J.
      • et al.
      F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.
      An SUVmax of ≤40 and 100 in the bladder for 68Ga-PSMA-617 and 68Ga-PSMA-11 has been reported, respectively.
      • Afshar-Oromieh A.
      • Malcher A.
      • Eder M.
      • et al.
      PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions.
      • Afshar-Oromieh A.
      • Hetzheim H.
      • Kratochwil C.
      • et al.
      The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions.
      • Pfob C.H.
      • Ziegler S.
      • Graner F.P.
      • et al.
      Biodistribution and radiation dosimetry of 68Ga-PSMA HBED CC—a PSMA specific probe for PET imaging of prostate cancer.
      • Afshar-Oromieh A.
      • Hetzheim H.
      • Kübler W.
      • et al.
      Radiation dosimetry of 68Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing.
      In contrast, the content of the urinary bladder was an SUVmax of 5 for 18F-PSMA-1007.
      • Giesel F.L.
      • Hadaschik B.
      • Cardinale J.
      • et al.
      F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.
      Performing 18-F-PSMA-1007 PET/CT at very low PSA levels potentially allows for more effective salvage treatment, because the prognosis is improved by the initiation of treatment before the PSA level has exceeded 0.5 ng/mL.
      • Suardi N.
      • Gandaglia G.
      • Gallina A.
      • et al.
      Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years.

      Conclusion

      Low urinary clearance of 18F-PSMA-1007 for PET/CT imaging provides additional diagnostic value in the case of local recurrence after radical prostatectomy that was considered unclear using standard mpMRI.

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