International Journal of Urology (2014) 21, 1286–1290
Urological Notes Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled ligand of prostate-speciﬁc membrane antigen: Promising novel option in prostate cancer imaging? Tobias Maurer M.D.,1* Ambros J Beer M.D.,2* Hans-Jürgen Wester M.D.,3 Hubert Kübler M.D.,1 Markus Schwaiger M.D.2 and Matthias Eiber M.D.2,4 Abbreviations & Acronyms 68 Ga-PSMA-L = 68Galliumlabeled ligand of prostate-specific membrane antigen ADC = apparent diffusion coefficient BS = bone scintigraphy CT = computed tomography DCE = dynamic contrast-enhanced Gs = Gleason score iAUC60 = initial area under the time-intensive curve (within 60 s) LN = lymph node(s) MBq = megabequerel MRI = magnetic resonance imaging PCa = prostate cancer PET = positron emission tomography PSMA = prostate-specific membrane antigen 1
Department of Urology, Department of Nuclear Medicine, 3Institute of Pharmaceutical Radiochemistry, 4 Institute of Diagnostic and Interventional Radiology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany [email protected]
*These two authors contributed equally to this work. DOI: 10.1111/iju.12577
Current imaging procedures for PCa, including PET, show considerable limitations and are not always able to meet the diagnostic needs.1 Recently, a 68Ga-PSMA-L has been introduced in PET imaging of PCa with first promising results.2 As a result of relatively exclusive expression of PSMA in prostatic tissue, as well as increased expression in PCa, 68Ga-PSMA-L was reported to show a favorable lesion-to-background ratio compared with the presently used choline-based PET examinations.3 Together with the novel development of combined PET/MRI, the combination of excellent morphological detail, multiparametric functional information, and molecular PET data might lead to a significant improvement in detection and staging of PCa, and thus could help to optimize oncological treatment.4–6 Here, based on our first clinical results, we describe 68 Ga-PSMA-L PET/MRI as a novel imaging technique for patients with PCa at different disease stages, and discuss potential future applications. Briefly, PET/MRI was carried out on a fully integrated whole-body hybrid PET/MRI system (Siemens Biograph mMR; Siemens Healthcare, Erlangen, Germany). After intravenous injection of 122 ± 17 MBq 68Ga-PSMA-L, a diagnostic PET-examination of the trunk (from base of skull to the proximal femur) with simultaneous acquisition of coronal T1-weighted and fat saturated axial T2-weighted images was carried out followed by a diagnostic multiparametric MR examination of the pelvis including a 15-min PET scan (mean time from injection to imaging: 51 min, range 45–63 min). To prevent extinction artifacts as a result of urinary excretion of the tracer, furosemide was applied and the bladder was emptied before the start of the examination. Case 1: A 72-year-old patient without evidence of malignancy in two prior biopsies, but highly suspected PCa (PSA 13.9 ng/mL, free-to-total ratio 6.9%, digital rectal examination normal) underwent 68Ga-PSMA-L PET/MRI and confirmation of a Gs 7b (4 + 3) PCa within the suspicious area on target biopsies without malignancy in the remaining biopsy cores (Fig. 1a–d). Case 2: A 72-year-old patient with biopsy-proven high-risk PCa was subjected to 68GaPSMA-L PET/MRI showing local tumor, but no evidence of metastatic disease (Fig. 1e,f). Postoperative histological analysis after radical prostatectomy showed a poorly differentiated PCa Gs 8 (4 + 4) of the left prostatic lobe with extracapsular extension without evidence of metastatic LN (pT3a pN0 [0/29] cM0 L0 V0 Pn1 G3 R0). Case 3: A 74-year-old patient with locally advanced high-risk PCa (PSA 12.9 ng/mL; Gs 9 [4 + 5]; cT3) and suspicion of pelvine LN metastases on CT, but negative results in bone scintigraphy (Fig. 1g) underwent further staging with 68Ga-PSMA-L PET/MRI. Besides the locally advanced tumor, multiple pelvine, retroperitoneal, and mediastinal and supraclavicular 68 Ga-PSMA-L-positive LN, two lesions in the right rib cage were also detected (Fig. 1h–j). Subsequently, initially favored local treatment was abandoned and antihormonal therapy was started. Case 4: A 74-year-old patient with biochemical recurrence 9 months after radical prostatectomy presenting with rising PSA (0.40 ng/mL; PSA nadir postoperatively 0.17 ng/mL; TNM stage at radical prostatectomy: pT3a pN0 cM0 R0 Gs 7a [3 + 4]; initial PSA 6.47 ng/mL) was staged with 68Ga-PSMA-L PET/MRI. A focal pararectal intense 68Ga-PSMA-L uptake could be detected corresponding to a normal-sized morphologically not suspicious LN (Fig. 1k,l). Therefore, irradiation therapy of the prostate bed and boost on suspicious LN was initiated with a subsequent drop of the PSA value. Based on these representative cases, we try to highlight the possible future applications of 68 Ga-PSMA-L PET/MRI. In patients with high suspicion, but without histological confirmation of PCa, multiparametric MRI is currently suggested for identification of suspicious areas to specifically target those lesions.7 In this setting, 68Ga-PSMA-L PET/MRI could provide additional molecular information, which together with the high-resolution anatomical images from MRI, could be used to target suspicious regions. In high-risk PCa, 68Ga-PSMA-L PET/MRI © 2014 The Japanese Urological Association
0 Fig. 1 Examples of 68Ga-PSMA-L PET/MRI imaging. (a–d) Axial T2-weighted sequence shows a diffuse hypointensity in the left posterior peripheral zone (dotted arrow in [a]), no diffusion restriction and no abnormalities in the parametric map of iAUC60 derived from DCE-sequences indicating postbioptic changes. In addition, a circumscript area of hypointensity can be found in the right anterior peripheral zone showing restricted diffusion in the corresponding ADC-map (arrows in [a] and [b]). The parametric map of iAUC60 shows a high wash-in rate in the corresponding part of the central zone (arrow in [c]). (d) 68Ga-PSMA-L PET/MRI-fused images show a focal high uptake of the tracer in this localization. Note, that residual air in the rectum (black strip surrounded by the bright signal from the ultrasound gel in [a]) resulted in (b) minor distortion of the ADC-map. (e) Axial T2-weighted sequence and (f) 68Ga-PSMA-L PET/MRI-fused images show a large tumor in the peripheral zone on the left side. Note that bulging of the capsule indicates extracapsular extension. (g) Bone scintigraphy was read as negative for bone metastases. (i) 68Ga-PSMA-L PET/MRI-fused images show two lesions of high focal uptake (arrows) corresponding to the origin of the 5 and 10 right ribs that are highly suggestive of bone metastases. (h) Exemplary periaortic enlarged LN on CT with (j) intense 68Ga-PSMA-L signal on PET/MRI-fused images highly suspicious for LN metastasis in the same patient. (k) Axial T2-weighted sequence shows an 6-mm pararectal LN, not suspicious because of its small size and atypical location. (i) 68Ga-PSMA-L PET/MRI-fused images show a high focal uptake projecting on that LN (left lower corner: color scale showing the standard-uptake values in 68Ga-PSMA-L PET/MRI-fused images [d], [f], [i], [j], [l]).
could enable a complete and more accurate staging of local tumor, LN involvement, and organ and bone metastases within one single examination superseding BS and further imaging procedures. Furthermore, in biochemical recurrent PCa 68GaPSMA-L PET/MRI could detect cancer sites more reliable at low PSA levels, rendering salvage irradiation therapy more effective. Thus, treatment plans and outcomes for patients with PCa could be improved. However, systematic and prospective evaluations of 68GaPSMA-L PET/MRI in PCa staging are mandatory. Only then reliable conclusions on the clinical value and potential of © 2014 The Japanese Urological Association
Ga-PSMA-L based PET/MRI be can drawn, or even recommendations for routine use can be disclosed.
Conﬂict of interest None declared.
References 1 Umbehr MH, Muntener M, Hany T, Sulser T, Bachmann LM. The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur. Urol. 2013; 64: 106–17.
2 Schafer M, Bauder-Wust U, Leotta K et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012; 2: 23. 3 Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur. J. Nucl. Med. Mol. Imaging 2012; 39: 1085–6. 4 Roethke MC, Kuru TH, Afshar-Oromieh A, Schlemmer HP, Hadaschik BA, Fenchel M. Hybrid positron emission tomography-magnetic resonance imaging with gallium 68 prostate-specific membrane antigen tracer: a next step for imaging of recurrent prostate cancer-preliminary results. Eur. Urol. 2013; 64: 862–4.
5 Drzezga A, Souvatzoglou M, Eiber M et al. First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses. J. Nucl. Med. 2012; 53: 845–55. 6 Arce-Calisaya P, Souvatzoglou M, Eiber M et al. Sensitivity of PET/MRI to detect recurrence of prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 2013; 40: 799. 7 Kuru TH, Roethke MC, Seidenader J et al. Critical evaluation of magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy for detection of prostate cancer. J. Urol. 2013; 190: 1380–6.
Editorial Comment Editorial Comment to Positron emission tomography/magnetic resonance imaging with 68 Gallium-labeled ligand of prostate-speciﬁc membrane antigen: Promising novel option in prostate cancer imaging? Magnetic resonance imaging (MRI) is regarded to be the superior method for prostate cancer imaging. This holds especially true for multiparametric MRI of the prostate, where different imaging sequences are combined in order to maximize information on tumor anatomy and physiology. Positron emission tomography (PET) imaging of the prostate is able to add a metabolic feature to the multiparametric approach; and with the introduction of fully integrated PET/MRI scanners, a real multiparametric/metabolic imaging approach of prostate cancer has become possible for the first time. Since the first report of simultaneous PET/MRI of prostate cancer, further studies have been carried out in this field.1 It was shown that 18F and 11C choline PET/MRI carried out well in comparison to PET/ computed tomography in terms of lesion detection and correlation of standardized uptake values.2,3 Furthermore, these studies showed the clinical feasibility and robustness of the integrated PET/MRI system when applied to prostate cancer imaging. Whereas some groups focus on “classical” tracers for prostate cancer PET/MRI imaging, such as 11C or 18F choline, other study groups explore the potentials of a Gallium-labeled prostate-specific membrane antigen ligand (68Ga-PSMA-L), which is overexpressed in prostate carcinoma cells when compared with other tissues expressing PSMA. Afshar-Oromieh et al. reported on an improved detection rate of lesions of suspected recurrent prostate cancer and improved tumor-tobackground ratio when using 68Ga-PSMA-L compared with 18F choline.4 In this Urological Note, Maurer et al. report on their first clinical results with 68Ga-PSMA-L simultaneous PET/MRI imaging of patients with prostate cancer at different disease stages.5 Their study gives an interesting brief overview of potential fields of application of 68Ga-PSMA-L in prostate cancer imaging with integrated PET/MRI. From a clinical point of view, the presented examples summarize and highlight problem fields of prostate cancer diagnostics; for example, a patient with previous negative prostate biopsies, but strong suspicion of prostate cancer, where precise biopsy planning is of utmost importance. 1288
Although the studies with the “new” prostate cancer tracer are indeed promising, recent reports on 18F choline as a tracer for prostate cancer imaging with combined PET/MRI are also encouraging.6 Considering the present literature and the examples presented by Maurer et al., prostate cancer imaging with 68 Ga-PSMA-L is a hot topic, but further prospective studies to show the expected superiority are required. Axel Wetter M.D. Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany [email protected]
Conﬂict of interest None declared.
References 1 Wetter A, Lipponer C, Nensa F et al. Simultaneous 18F choline positron emission tomography/magnetic resonance imaging of the prostate: initial results. Invest. Radiol. 2013; 48: 256–62. 2 Wetter A, Lipponer C, Nensa F et al. Evaluation of the PET component of simultaneous [(18)F]choline PET/MRI in prostate cancer: comparison with [(18)F]choline PET/CT. Eur. J. Nucl. Med. Mol. Imaging 2014; 41: 79–88. 3 Souvatzoglou M, Eiber M, Takei T et al. Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 2013; 40: 1486–99. 4 Afshar-Oromieh A, Zechmann C, 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. Eur. J. Nucl. Med. Mol. Imaging 2014; 41: 11–20. 5 Maurer T, Beer AJ, Wester HJ, Kübler H, Schwaiger M, Eiber M. Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled ligand of prostate-specific membrane antigen: promising novel option in prostate cancer imaging? Int. J. Urol. 2014; 21: 1286–8. 6 De Perrot T, Rager O, Scheffler M et al. Potential of 18F-fluorcholine PET/MRI for prostate cancer imaging. Eur. J. Nucl. Med. Mol. Imaging 2014; 41: 1744–55. © 2014 The Japanese Urological Association