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.

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.

Since the mid-1990s, ¹⁸F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future.

The short half-life of existing prostate-specific membrane antigen (PSMA) tracers limits their time for internalization into tumor cells after injection, which is an essential prerequisite for robust detection of tumor lesions with low PSMA expression on PET/CT scans. Due to its longer half-life, the ⁸⁹Zr-labeled ligand ⁸⁹Zr-PSMA-Df allows acquisition of PET scans up to 6 days after injection, thereby overcoming the above limitation. We investigated whether ⁸⁹Zr-PSMA-Df allowed more sensitive detection of weak PSMA-positive prostate cancer lesions. Methods: We selected 14 prostate cancer patients with biochemical recurrence who exhibited no PSMA-positive lesions on a PET scan acquired with existing PSMA tracers (⁶⁸Ga-PSMA-11, ¹⁸F-JK-PSMA-7). Within 5 weeks after the negative scan, we performed a second PSMA-PET scan using ⁸⁹Zr-PSMA-Df (117±16 MBq, PET acquisition within 6 days of injection). Results:⁸⁹Zr-PSMA-Df detected 15 PSMA-positive lesions in 8/14 patients, who had a PET-negative reading of their initial PET scans with existing tracers. In these 8 patients, the new scans revealed localized recurrence of disease (3/8), metastases in lymph nodes (3/8), or lesions at distant sites (2/8). Based on these results, patients received lesion-targeted radiotherapies (5/8), androgen deprivation therapies (2/8), or no therapy (1/8). The plausibility of 14/15 lesions was supported by histology, clinical follow-up after radiotherapy or subsequent imaging. Furthermore, comparison of the 15 ⁸⁹Zr-PSMA-Df-positive lesions with their correlates on the original PET scan revealed that established tracers exhibited mild accumulation in 7/15 lesions but contrast-to-noise ratios (CNR) were too low for robust detection of these lesions (CNR 2.4±3.7 for established tracers vs. 10.2±8.5 for ⁸⁹Zr-PSMA-Df, P = 0.0014). The SUV_max of the 15 ⁸⁹Zr-PSMA-Df-positive lesions (11.5±5.8) was significantly higher than the SUV_max on the original PET scans (4.7±2.8, P = 0.0001). Kidneys were the most exposed organ with doses of 3.3±0.7 mGy/MBq. The effective dose was 0.15±0.04 mSv/MBq. Conclusion: In patients with weak PSMA expression, a longer period of time might be needed for ligand internalization than that offered by existing PSMA tracers to make lesions visible on PET/CT scans. Hence, ⁸⁹Zr-PSMA-Df might be of significant benefit to patients in whom the search for weak PSMA-positive lesions is challenging. Radiation exposure should be weighed against the potential benefit of metastasis-directed therapy or salvage radiotherapy, which we initiated in 36% (5/14) of our patients based on their ⁸⁹Zr-PSMA-Df PET scans.

In preclinical trials, the recently developed tracer 2-methoxy-18F-DCFPyL (18F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of 18F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. Methods: In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with 18F-JK-PSMA-7 was directly compared with 68Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical 18F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). Results: The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that 18F-JK-PSMA-7 was at least equivalent to 68Ga-PSMA-11. All unequivocally 68Ga-PSMA-11-positive lesions could be also detected using 18F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of 18F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)-stratified detection rate of 18F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 μg/L), 87.5% (14/16 patients; PSA 0.5-2 μg/L), and 90.9% (20/22 patients; PSA > 2 μg/L). Conclusion: The tracer 18F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that 18F-JK-PSMA-7 was not inferior when directly compared with 68Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, 18F-JK-PSMA-7 was useful in tumor localization. 18F-JK-PSMA-7 is recommended for future prospective trials.

We investigated the whole-body distribution and the radiation dosimetry of [18F]-JK-PSMA-7, a novel 18F-labeled PSMA-ligand for PET/CT imaging of prostate cancer. Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [18F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of tumor-to-background ratios (TBR’s). Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [18F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUVmax and SUVpeak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUVmax and SUVpeak within the PSMA-positive lesions was observed. The highest TBR of [18F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations.