Purpose Gallium-68 (Ga-68)-labeled tracers for imaging expression of the prostate-specific membrane antigen (PSMA) such as the [⁶⁸Ga]Ga-PSMA-HBED-CC have already demonstrated high potential for the detection of recurrent prostate cancer. However, compared to Ga-68, a labeling with fluorine-18 (F-18) would offer advantages with respect to availability, production amount, and image resolution. [¹⁸F]DCFPyL is a promising F-18-labeled candidate for PSMA-positron emission tomography (PET) imaging that has been recently introduced. In the current study, we aimed to compare [⁶⁸Ga]Ga-PSMA-HBED-CC and [¹⁸F]DCFPyL for clinical use in biochemically relapsed prostate cancer. Procedures In 14 selected patients with PSA relapse of prostate cancer, [¹⁸F]DCFPyL PET/X-ray computed tomography (CT) was performed in addition to [⁶⁸Ga]Ga-PSMA-HBED-CC PET/CT. A systematic comparison was carried out between results obtained with both tracers with regard to the number of detected PSMA-positive lesions, the standardized uptake value (SUV)_max and the lesion to background ratios. Results All suspicious lesions identified by [⁶⁸Ga]Ga-PSMA-HBED-CC were also detected with [¹⁸F]DCFPyL. In three patients, additional lesions were observed using [¹⁸F]DCFPyL PET/CT. The mean SUV_max in the concordant [¹⁸F]DCFPyL PSMA-positive lesions was significantly higher as compared to [⁶⁸Ga]Ga-PSMA-HBED-CC (14.5 vs. 12.2, p = 0.028, n = 15). The mean tumor to background ratios (n = 15) were significantly higher for [¹⁸F]DCFPyL compared to [⁶⁸Ga]Ga-PSMA-HBED-CC using kidney, spleen, or parotid as reference organs (p = 0.006, p = 0.002, p = 0.008), but no significant differences were found using the liver (p = 0.167) or the mediastinum (p = 0.363) as reference organs. Conclusion [¹⁸F]DCFPyL PET/CT provided a high image quality and visualized small prostate lesions with excellent sensitivity. [¹⁸F]DCFPyL represents a highly promising alternative to [⁶⁸Ga]Ga-PSMA-HBED-CC for PSMA-PET/CT imaging in relapsed prostate cancer.

Several studies outlined the sensitivity of ⁶⁸Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with ¹⁸F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the ¹⁸F-labeled PSMA tracer ¹⁸F-DCFPyL and the ⁶⁸Ga-labeled reference ⁶⁸Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using ¹⁸F-DCFPyL (n = 62, 269.8 MBq, PET scan at 120 min after injection) or ⁶⁸Ga-PSMA-HBED-CC (n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy (n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels (P = 4.3 × 10⁻³). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L (P = 2.4 × 10⁻⁵). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage (P = 3.4 × 10⁻⁶). For a PSA of 0.5–3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for ¹⁸F-DCFPyL and 66% (23/35) for ⁶⁸Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy (n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of ¹⁸F-DCFPyL and ⁶⁸Ga-PSMA-HBED-CC were strongly comparable (P = 2.71 × 10⁻⁸). However, in 36% of the PSMA-positive patients we detected additional lesions on the ¹⁸F-DCFPyL scan (P = 3.7 × 10⁻²). Conclusion: Our data suggest that ¹⁸F-DCFPyL is noninferior to ⁶⁸Ga-PSMA-HBED-CC, while offering the advantages of ¹⁸F labeling. Our results indicate that imaging with ¹⁸F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for ¹⁸F-DCFPyL and ⁶⁸Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of ¹⁸F-DCFPyL in future prospective trials.

A novel radiofluorination procedure using only precursor and [¹⁸F]fluoride without the need for azeotropic drying, base and other ingredients was developed.

¹⁸F-Prostate-specific membrane antigen (PSMA)-1007 is mainly excreted through the liver. We benchmarked the performance of ¹⁸F-PSMA-1007 against three renally excreted PSMA-tracers. Methods: Among 668 patients we selected 27 patients in whom the PET/CT with ⁶⁸Ga-PSMA-11, ¹⁸F-DCFPyL, or ¹⁸F-JK-PSMA-7 was interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within <3 weeks, a second PET scan with ¹⁸F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive loco-regional findings was scored on a 5-point scale, first in routine diagnostics (reader 1), then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast enhanced MRI. Results: For both readers, ¹⁸F-PSMA-1007 facilitated the interpretability of 27 loco-regional lesions. In PET-2, the clinical read-out led to a significantly lower number of equivocal loco-regional lesions (P = 0.024), reader 2 reported a significantly higher rate of suspicious lesions that were falsely interpreted as probably benign in PET-1 (P = 0.023). Exclusively on PET-2, we observed a total of 15 PSMA-positive PSMA-spots in the bone marrow of 6 patients (= 22%). None of the 15 discordant spots had a morphological correlate on the corresponding CT or on the subsequent MRI. Thus, ¹⁸F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots (P = 0.0006). Conclusion: ¹⁸F-PSMA-1007 may increase confidence to interpret small loco-regional lesions adjacent to the urinary tract. However, it may decrease the interpretability of skeletal lesions.