Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

Abstract

The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, 68 Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of 68 Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. Methods: Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2-59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of 68 Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. Results: Two hundred twenty-two (89.5%) patients showed pathologic findings in 68 Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of $2, 1 to ,2, 0.5 to ,1, and 0.2 to ,0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in ,1, 1 to ,2, 2 to ,5, and $5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in .6, 4-6, and ,4 mo, respectively). 68 Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (#7 vs. $8), detection efficacy was significantly increased (P 5 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P 5 0.0783). Conclusion: Hybrid 68 Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (,0.5 ng/mL), which in many cases can substantially influence the further clinical management.

Estimation of radiation dosimetry for 68Ga-HBED-CC (PSMA-11) in patients with suspected recurrence of prostate cancer

“…The [ 68 Ga]Ga-HBED-CC (PSMA-11) radiopharmaceutical has been shown to be useful in the detection of tumor recurrence in prostate cancer patients previously treated with prostatectomy or radiation therapy [1,2], with lesion detectability appearing to be better than we can achieve with [ 11 C]acetate PET/CT. [ 68 Ga]Ga-HBED-CC (PSMA-11) has a relatively low molecular weight (1014 g/mole), and targets the cell surface prostatespecific membrane antigen (PSMA) with the urea fragment of the Glu-urea-Lys(Ahx)-HBED-CC conjugate [9].…”

“…The PSMA-targeted [ 68 Ga]Ga-HBED-CC (PSMA-11) radiopharmaceutical has been shown to be quite useful in imaging patients with prostate cancer to define the location and extent of disease [1][2]. However, despite its fairly extensive human use of [ 68 Ga]Ga-HBED-CC, until recently no estimates of the human radiation dosimetry for [ 68 Ga]Ga-HBED-CC were available in the published literature.…”

Impact of 18F-Fluciclovine PET on Target Volume Definition for Postprostatectomy Salvage Radiotherapy: Initial Findings from a Randomized Trial

“…In this context, 18 F-fluciclovine (anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid), which is transported in a manner similar to glutamine, has shown promising imaging characteristics for the detection of prostate cancer recurrence. 18 F-fluciclovine PET/CT has been compared with radioimmunoscintigraphy in a randomized trial and has shown significantly higher accuracy (22,23).…”

“…In this randomized, prospective intention-to-treat clinical trial, we set out to determine whether incorporating information from 18 F-fluciclovine PET into treatment planning significantly changes the volumes targeted for salvage therapy in patients with rising levels of PSA after prostatectomy and whether there is an effect on surrounding normal structures and acute toxicity. Our hypotheses were that the target volumes would be significantly modified and that acute toxicity would not increase.…”

“…The investigational classes of radiotracers include fatty acid analogs (acetate), cell membrane analogs (choline), amino acid analogs (fluciclovine), and newer-generation prostate-specific membrane antigen ligands (16)(17)(18)(19)(20)(21). In this context, 18 F-fluciclovine (anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid), which is transported in a manner similar to glutamine, has shown promising imaging characteristics for the detection of prostate cancer recurrence. 18 F-fluciclovine PET/CT has been compared with radioimmunoscintigraphy in a randomized trial and has shown significantly higher accuracy (22,23).…”