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.

Gallium 68–labeled fibroblast activation protein inhibitor PET is an oncologic imaging strategy based on the molecular targeting of fibroblast activation protein highly expressed in the stroma of e... Gallium 68 (68Ga)–labeled fibroblast activation protein (FAP) inhibitor (FAPI) PET is based on the molecular targeting of the FAP, which is known to be highly expressed in the major cell population...

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.

Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [¹⁸F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

Background: ⁶⁸Ga-prostate-specific membrane antigen (PSMA)-11-positron-emission-tomography (PET)/ computer-tomography (CT) represents an advanced method for staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, due to the narrow availability of ⁶⁸Ga the development of alternative tracers is of high interest. Objective: To examine the value of the new PET tracer ¹⁸F-PSMA-1007 for staging of local disease by comparing it to multiparametric magnetic resonance imaging (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, ¹⁸F-PSMA-1007-PET/CT was performed in 10 men with biopsy confirmed high-risk prostate cancer (PCa). 9 patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA-staining was added for representative sections in RP specimen slices. Localization and agreement analysis of ¹⁸F-PSMA-1007-PET/CT, mpMRI and RP specimen was done dividing the prostate into 38 sections as described in PI-RADS v2. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and accuracy were calculated for total and near total agreement. Results: ¹⁸F-PSMA-1007-PET/CT had an NPV of 68% and 75% accuracy and mpMRI had an NPV of 88% and 73% accuracy for total agreement. Near total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for ¹⁸F-PSMA-1007-PET/CT and 90% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near total agreement. Conclusion: Comparison with RP histopathology demonstrates that ¹⁸F-PSMA-1007 PET/CT is promising for accurate local staging of PCa.

Informed consent Written informed consent for imaging with an experimental tracer and publication of the individual patient history was obtained.