Comparative Evaluation of (¹⁸F)AlF-PSMA-HBED-CC and ⁶⁸Ga-PSMA-HBED-CC in Staging Intermediate-/High-Risk Prostate Cancer: A Prospective Study

Abstract

Objective ⁶⁸Ga-PSMA-HBED-CC positron emission tomography (PET)/computed tomography (CT) represents a clinically relevant technique for the evaluation of prostate cancer (PCa) patients, whereas ¹⁸F-AIF-PSMA-HBED-CC is a novel tracer produced in our center, with suitable radiochemical purity for clinical purposes. We prospectively compared the diagnostic values of both tracers for the detection of metastatic disease in patients with intermediate-/high-risk PCa at initial staging.

Materials and Methods Sixty-six patients (mean age: 63 years; range: 52–78 years) with PCa at initial staging (Gleason score ≥6; median prostate-specific antigen [PSA]: 10 ng/mL; range:1.7–152 ng/mL) prospectively underwent routine ⁶⁸Ga-PSMA-11 and ¹⁸F-AlF-PSMA-11 PET/CT scanning with a 64-slice PET/CT scan with time-of-flight (TOF) correction. We measured the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) in all coincidentally detected lesions. Open prostatectomy and pelvic lymph node dissection were performed in nonmetastatic patients. Histopathology, correlative imaging, and/or clinical follow-up were considered the gold standard. Follow-up was conducted at least 4 months after PET/CT scanning (median: 6.4 months; range: 4–11 months). Sensitivity, specificity, and predictive values were calculated.

Results The overall detection rate was 85% (56/66) for both tracers. At least one suspicious lesion indicating potential PCa metastasis was detected in 20 (30%) and 21 (32%) of 66 patients for ⁶⁸Ga-PSMA-11 and ¹⁸F-AIF-PSMA-11 tracers, respectively. A total of 145 extra-prostatic lesions were detected in the bone (n = 56), lymph nodes (n = 88), and lung (n = 1) by at least one radiopharmaceutical: 131 (90%) for ⁶⁸Ga-PSMA-11 and 123 (85%) for ¹⁸F-AlF-PSMA-11.

In concordant lesions, a significant correlation was found between the SUVmax of both tracers (r = 0.90, p = 0.001). The SUVmax and LBR for ¹⁸F-AlF-PSMA-11 were higher in bone foci (n = 39) compared with ⁶⁸Ga-PSMA-11 (7.2 vs. 8.9 and 14 vs. 13, respectively, p = 0.02).

For the detection of systemic metastasis, the sensitivity values were the same for both techniques: 0.90 (95% confidence interval [CI]: 0.68–0.98). We calculated specificities of 0.96 (95% CI: 0.85–0.99) and 0.94 (95% CI: 0.82–0.98) for ⁶⁸Ga-PSMA-11 and ¹⁸F-AlF-PSMA-11, respectively.

Conclusions ⁶⁸Ga-PSMA-11 and ¹⁸F-AlF-PSMA-11 PET/CT seem to be clinically equivalent imaging techniques for the assessment of primary intermediate-/high-risk PCa with promising potential for the detection of metastatic spread that would impact patient management.

Keywords

high-risk prostate cancer - initial staging - ¹⁸F-AlF-PSMA-11 - ⁶⁸Ga-PSMA-11 - PET/CT

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Publication History

Article published online:
21 January 2025

• References

• 1 Ferlay J, Soerjomataram I, Dikshit R. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136 (05) E359-E386
• 2 McKay RR, Feng FY, Wang AY, Wallis CJD, Moses KA. Recent advances in the management of high-risk localized prostate cancer: local therapy, systemic therapy, and biomarkers to guide treatment decisions. Am Soc Clin Oncol Educ Book 2020; 40: 1-12
• 3 SEET. Cancer Stat Facts: Prostate Cancer. 2020. Accessed January 5, 2025 at: https://seer.cancer.gov/statfacts/html/prost.html
• 4 Steiner Ch, Vees H, Zaidi H. et al. Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence. Nuklearmedizin 2009; 48 (01) 1-9 , quiz N2–N3
• 5 Afshar-Oromieh A, Zechmann CM, Malcher A. et al. Comparison of PET imaging with a ⁽⁶⁸⁾Ga-labelled PSMA ligand and ⁽¹⁸⁾F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41 (01) 11-20
• 6 Eder M, Schäfer M, Bauder-Wüst U. et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012; 23 (04) 688-697
• 7 Dietlein M, Kobe C, Kuhnert G. et al. Comparison of [⁽¹⁸⁾F]DCFPyL and [⁽⁶⁸⁾Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol 2015; 17 (04) 575-584
• 8 Mease RC, Dusich CL, Foss CA. et al. N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[¹⁸F]fluorobenzyl-L-cysteine, [¹⁸F]DCFBC: a new imaging probe for prostate cancer. Clin Cancer Res 2008; 14 (10) 3036-3043
• 9 Giesel FL, Hadaschik B, Cardinale J. et al. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging 2017; 44 (04) 678-688
• 10 Giglio J, Zeni M, Savio E, Engler H. Synthesis of an Al¹⁸F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform. EJNMMI Radiopharm Chem 2018; 3 (01) 4
• 11 D'Amico AV, Whittington R, Malkowicz SB. et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280 (11) 969-974
• 12 Afshar-Oromieh A, Avtzi E, Giesel FL. et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42 (02) 197-209
• 13 Ceci F, Oprea-Lager DE, Emmett L. et al. E-PSMA: the EANM standardized reporting guidelines v1.0 for PSMA-PET. Eur J Nucl Med Mol Imaging 2021; 48 (05) 1626-1638
• 14 Rowe SP, Pienta KJ, Pomper MG, Gorin MA. PSMA-RADS version 1.0: a step towards standardizing the interpretation and reporting of PSMA-targeted PET imaging studies. Eur Urol 2018; 73 (04) 485-487
• 15 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 (10) 1486-1499
• 16 Evangelista L, Guttilla A, Zattoni F, Muzzio PC, Zattoni F. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol 2013; 63 (06) 1040-1048
• 17 Afshar-Oromieh A, Haberkorn U, Schlemmer HP. et al. Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 2014; 41 (05) 887-897
• 18 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. Eur J Nucl Med Mol Imaging 2013; 40 (04) 486-495
• 19 Kratochwil C, Giesel FL, Stefanova M. et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with ¹⁷⁷Lu-labeled PSMA-617. J Nucl Med 2016; 57 (08) 1170-1176
• 20 Alonso O, Dos Santos G, García Fontes M, Balter H, Engler H. ⁶⁸Ga-PSMA and ¹¹C-choline comparison using a tri-modality PET/CT-MRI (3.0 T) system with a dedicated shuttle. Eur J Hybrid Imaging 2018; 2 (01) 9
• 21 Eiber M, Fendler WP, Rowe SP. et al. Prostate-specific membrane antigen ligands for imaging and therapy. J Nucl Med 2017; 58 (Suppl. 02) 67S-76S
• 22 Chen Y, Pullambhatla M, Foss CA. et al. 2-(3-1-carboxy-5-[(6-[¹⁸F]fluoro-pyridine-3-carbonyl)-amino]-pentyl-ureido)-pentanedioic acid, [¹⁸F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res 2011; 17 (24) 7645-7653
• 23 Yu C, Pan D, Mi B. et al. ⁽¹⁸⁾F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases. Eur J Nucl Med Mol Imaging 2015; 42 (13) 2021-2028
• 24 Allott L, Da Pieve C, Turton DR, Smith G. A general (¹⁸F)AlF radiochemistry procedure on two automated synthesis platforms. React Chem Eng 2017; 2 (01) 68-74
• 25 Lütje S, Franssen GM, Herrmann K. et al. In vitro and in vivo characterization of an ¹⁸F-AlF-labeled PSMA ligand for imaging of PSMA-expressing xenografts. J Nucl Med 2019; 60 (07) 1017-1022
• 26 Ioppolo JA, Nezich RA, Richardson KL, Morandeau L, Leedman PJ, Price RI. Direct in vivo comparison of [¹⁸F]PSMA-1007 with [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]AlF-PSMA-11 in mice bearing PSMA-expressing xenografts. Appl Radiat Isot 2020; 161: 109164
• 27 Li X, Yu M, Yang J. et al. [¹⁸F]AlF-PSMA-11 PET in diagnosing prostate cancer: a head-to-head comparison with [⁶⁸Ga]Ga-PSMA-11 PET and an exploration of dual-phase scanning. Eur J Nucl Med Mol Imaging 2024; 8 (01) 28
• 28 Virgolini I, Decristoforo C, Haug A, Fanti S, Uprimny C. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging 2018; 45 (03) 471-495
• 29 Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol 2016; 13 (04) 226-235
• 30 Hirmas N, Al-Ibraheem A, Herrmann K. et al. [⁶⁸Ga]PSMA PET/CT improves initial staging and management plan of patients with high-risk prostate cancer. Mol Imaging Biol 2019; 21 (03) 574-581
• 31 Maurer T, Gschwend JE, Rauscher I. et al. Diagnostic efficacy of ⁽⁶⁸⁾gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195 (05) 1436-1443
• 32 Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998; 82 (11) 2256-2261
• 33 Heidenreich A, Bastian PJ, Bellmunt J. et al; European Association of Urology. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014; 65 (01) 124-137
• 34 Hoffmann MA, Miederer M, Wieler HJ, Ruf C, Jakobs FM, Schreckenberger M. Diagnostic performance of ⁶⁸gallium-PSMA-11 PET/CT to detect significant prostate cancer and comparison with ¹⁸FEC PET/CT. Oncotarget 2017; 8 (67) 111073-111083
• 35 Koerber SA, Utzinger MT, Kratochwil C. et al. ⁶⁸Ga-PSMA-11 PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med 2017; 58 (12) 1943-1948
• 36 Steuber T, Schlomm T, Heinzer H. et al. [F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study. Eur J Cancer 2010; 46 (02) 449-455
• 37 Budäus L, Leyh-Bannurah SR, Salomon G. et al. Initial experience of ⁽⁶⁸⁾Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69 (03) 393-396
• 38 Haffner MC, Kronberger IE, Ross JS. et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 2009; 40 (12) 1754-1761
• 39 De Coster L, Sciot R, Everaerts W. et al. Fibrous dysplasia mimicking bone metastasis on ⁶⁸GA-PSMA PET/MRI. Eur J Nucl Med Mol Imaging 2017; 44 (09) 1607-1608
• 40 Krohn T, Verburg FA, Pufe T. et al. [(68)Ga]PSMA-HBED uptake mimicking lymph node metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur J Nucl Med Mol Imaging 2015; 42 (02) 210-214