Purpose The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer ⁶⁸Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, ⁶⁸Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of ¹⁸F-labelled analogs. ¹⁸F-PSMA-1007 was selected among several ¹⁸F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of ¹⁸F-PSMA-1007 in human volunteers and patients. Methods Radiation dosimetry of ¹⁸F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent ¹⁸F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining. Results With an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, ¹⁸F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other ¹⁸F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, ¹⁸F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to ¹⁸F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. ¹⁸F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. Conclusion ¹⁸F-PSMA-1007 performs at least comparably to ⁶⁸Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of ⁶⁸Ga-labelled PSMA-targeted tracers.

Purpose: Since the clinical introduction of ⁶⁸Ga-PSMA-11 PET/CT, this imaging method has rapidly spread and is now regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to analyse the influence of several variables with possible influence on PSMA ligand uptake in a large cohort. Methods: We performed a retrospective analysis of 1007 consecutive patients who were scanned with ⁶⁸Ga-PSMA-11 PET/CT (1 h after injection) from January 2014 to January 2017 to detect recurrent disease. Patients with untreated primary PCa or patients referred for PSMA radioligand therapy were excluded. The possible effects of different variables including PSA level and PSA doubling time (PSA_DT), PSA velocity (PSA_Vel), Gleason score (GSC, including separate analysis of GSC 7a and 7b), ongoing androgen deprivation therapy (ADT), patient age and amount of injected activity were evaluated. Results: In 79.5% of patients at least one lesion with characteristics suggestive of recurrent PCa was detected. A pathological (positive) PET/CT scan was associated with PSA level and ADT. GSC, amount of injected activity, patient age, PSA_DT and PSA_Vel were not associated with a positive PET/CT scan in multivariate analysis. Conclusion: ⁶⁸Ga-PSMA-11 PET/CT detects tumour lesions in a high percentage of patients with recurrent PCa. Tumour detection is clearly associated with PSA level and ADT. Only a tendency for an association without statistical significance was found between higher GSC and a higher probability of a pathological PET/CT scan. No associations were found between a pathological ⁶⁸Ga-PSMA-11 PET/CT scan and patient age, amount of injected activity, PSA_DT or PSA_Vel.

Purpose: PET-imaging with the prostate-specific membrane antigen-targeted radioligand ⁶⁸Ga-PSMA-11 is regarded as a significant step forward in the diagnosis of prostate cancer (PCa). More recently, a PSMA-ligand was developed which can be labeled with ⁶⁸Ga, ¹¹¹In, ¹⁷⁷Lu, and ⁹⁰Y. This ligand, named PSMA-617, therefore enables both, diagnosis and therapy of PCa. The aim of this evaluation was to clinically investigate the distribution of ⁶⁸Ga-PSMA-617 in normal tissues and in PCa lesions as well as to evaluate the radiation exposure by the radioligand in PET-imaging. Methods: Nineteen patients, most of them with recurrent PCa, were referred to ⁶⁸Ga-PSMA-617-PET/CT. Quantitative assessment of tracer uptake of several organs and of 53 representative tumor lesions was performed in 15 patients at 1h and 3h post injection (p.i.). In four additional patients, the same procedure was conducted at 5min, 1h, 2h, 3h, 4h and 5h p.i. Based on the data of these four patients (mean injected dose of 231 MBq) the radiation exposure of a ⁶⁸Ga-PSMA-617-PET/CT was identified. Results: Intense tracer uptake was observed in kidneys and salivary glands. In 14 of 19 patients (73.7%) at least one tumor suspicious lesion was detected at 3h p.i. Of 53 representative tumor lesions selected at 3h p.i., 47 lesions were visible at 1h p.i. Mean tumor-to-background ratio for SUV_max was 20.4 ± 17.3 (2.3 – 84.0) at 1h p.i. and 38.2 ± 38.6 (3.6 – 154.3) at 3h p.i. Average radiation exposure (effective dose) was approximately 0.021 mSv/MBq. Conclusion: Within healthy organs, kidneys and salivary glands showed the highest ⁶⁸Ga-PSMA-617 uptake. The radiation exposure is relatively low. ⁶⁸Ga-PSMA-617 shows PCa-lesions with very high contrast. Images conducted between 2-3h p.i. seem to be the best option with regard to radiotracer uptake and tumor contrast. Later images can help to clarify unclear lesions.

The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. ⁶⁸Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([⁶⁸Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective ⁶⁸Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx) pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [⁶⁸Ga]Ga-PSMA-HBED-CC.

Prostate-specific membrane antigen (PSMA)–targeted PET imaging recently emerged as a new method for the staging and restaging of prostate cancer. Most published studies investigated the diagnostic potential of ⁶⁸Ga-labeled PSMA agents that are excreted renally. ¹⁸F-PSMA-1007 is a novel PSMA ligand that has excellent preclinical characteristics and that is only minimally excreted by the urinary tract, a potential advantage for pelvic imaging. The aim of this study was to investigate the diagnostic efficacy of ¹⁸F-PSMA-1007 for biochemical recurrence (BCR) after radical prostatectomy. Methods: From 3 academic centers, 251 patients with BCR after radical prostatectomy were evaluated in a retrospective analysis. Patients who had received second-line androgen deprivation therapy (ADT) or chemotherapy were excluded, but prior first-line ADT exposure was allowed. The median prostate-specific antigen (PSA) level was 1.2 ng/mL (range, 0.2–228 ng/mL). All patients underwent PSMA PET/CT at 92 ± 26 min after injection of 301 ± 46 MBq of ¹⁸F-PSMA-1007. The rate of detection of presumed recurrence sites was correlated with the PSA level and original primary Gleason score. A comparison to a subset of patients treated previously with ADT was undertaken. Results: Of the 251 patients, 204 (81.3%) had evidence of recurrence on ¹⁸F-PSMA-1007 PET/CT. The detection rates were 94.0% (79/84), 90.9% (50/55), 74.5% (35/47), and 61.5% (40/65) for PSA levels of greater than or equal to 2, 1 to less than 2, 0.5 to less than 1, and 0.2 to less than 0.5 ng/mL, respectively. ¹⁸F-PSMA-1007 PET/CT revealed local recurrence in 24.7% of patients (n = 62). Lymph node metastases were present in the pelvis in 40.6% of patients (n = 102), in the retroperitoneum in 19.5% of patients (n = 49), and in supradiaphragmatic locations in 12.0% of patients (n = 30). Bone and visceral metastases were detected in 40.2% of patients (n = 101) and in 3.6% of patients (n = 9), respectively. In tumors with higher Gleason scores (≤7 vs. ≥8), detection efficacy trended higher (76.3% vs. 86.7%) but was not statistically significant (P = 0.32). However, detection efficacy was higher in patients who had received ADT (91.7% vs. 78.0%) within 6 mo before imaging (P = 0.0179). Conclusion: ¹⁸F-PSMA-1007 PET/CT offers high detection rates for BCR after radical prostatectomy that are comparable to or better than those published for ⁶⁸Ga-labeled PSMA ligands.

Introduction: In recent years several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Few of those had a high clinical impact for the treatment of patients suffering from prostate cancer. However, the number of fluorine-18 labeled tracers addressing PSMA is still limited. Therefore, we aimed at the development of a radiofluorinated molecule with emphasis on resembling the structure of the therapeutic PSMA-617. Methods: The non-radioactive reference compound PSMA-1007 and the labeling precursor were built up by solid phase chemistry. The radioligand ¹⁸F-PSMA-1007 was produced via a two-step procedure using the prosthetic group 6-¹⁸F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester (6-¹⁸F-F-Py-TFP). The binding affinity of the ligand towards PSMA and its internalization properties were evaluated in vitro using PSMA-positive LNCaP (Lymph Node Carcinoma of the Prostate) cells. Further, organ distribution studies were performed using LNCaP- and PC-3 (Prostate Cancer cell line; PSMA negative) tumor bearing mice. Finally, a microPET (small animal Positron Emission Tomography) imaging with an LNCaP tumor bearing mouse was carried out. Results: The identified ligand revealed a binding affinity of 6.7±1.7 nM towards PSMA and an exceptional high internalization ratio of 67±13 % in vitro. In organ distribution studies a high and specific tumor uptake of 8.0±2.4 %ID/g in LNCaP tumor bearing mice was observed. In further microPET experiments LNCaP tumors were clearly visualized. Conclusion: The radiofluorinated PSMA-ligand showed promising characteristics in its preclinical evaluation and the feasibility of prostate cancer imaging was demonstrated by microPET studies. Thus, we recommend the ligand ¹⁸F-PSMA-1007 for clinical transfer as diagnostic PET tracer for prestaging and monitoring of prostate cancer.