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As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera® was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera® combines the radionuclide 177Lu with the somatostatin analogue DOTA-TATE, thus delivering ionizing radiation specifically to tumor cells expressing somatostatin receptors. As a result, DNA single- and double-strand breaks are provoked, in case of double-strand breaks leading to cell death of the tumor and its SSTR-positive lesions.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of 68 Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of 68 Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Immune checkpoint inhibitor (ICI) therapy has emerged as a major treatment option for a variety of cancers. Among the immune checkpoints addressed, the programmed death receptor 1 (PD-1) and its ligand PD-L1 are the key targets for an ICI. PD-L1 has especially been proven to be a reproducible biomarker allowing for therapy decisions and monitoring therapy success. However, the expression of PD-L1 is not only heterogeneous among and within tumor lesions, but the expression is very dynamic and changes over time. Immunohistochemistry, which is the standard diagnostic tool, can only inadequately address these challenges. On the other hand, molecular imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) provide the advantage of a whole-body scan and therefore fully address the issue of the heterogeneous expression of checkpoints over time. Here, we provide an overview of existing PET, SPECT, and optical imaging (OI) (radio)tracers for the imaging of the upregulation levels of PD-1 and PD-L1. We summarize the preclinical and clinical data of the different molecule classes of radiotracers and discuss their respective advantages and disadvantages. At the end, we show possible future directions for developing new radiotracers for the imaging of PD-1/PD-L1 status in cancer patients.

Purpose The clinical introduction of 68 Ga-PSMA-11 (“HBED-CC”) ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection. Methods Four patients with recurrent PCa were referred for 68 Ga-PSMA-11 PET/CT. Whole-body PET/CT low-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152–198 MBq 68 Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time–activity curves were created for each source organ as well as for the remainder. The radiation exposure of a 68 Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases. Results The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262 ± 0.098 mGy/MBq, liver 0.031 ± 0.004 mGy/MBq, upper large intestine 0.054 ± 0.041 mGy/MBq, urinary bladder 0.13 ± 0.059 mGy/MBq. The calculated mean effective dose was 0.023 ± 0.004 mSv/MBq (=0.085 ± 0.015 rem/mCi). Most tumor lesions ( n  = 16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.). Conclusions The mean effective dose of a 68 Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for 68 Ga-PSMA-11 PET/CT in this patient cohort.

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.

The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress. A particular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g., for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes as well as their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.

BackgroundThe analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. MethodsA retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed.ResultsDifferences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%).ConclusionIn terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

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.

For the PET imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. [18F]PSMA-1007, a radiopharmaceutical labeled with fluorine-18, has excellent properties for the detection of prostate cancer. Essential for the human use of a radiotracer is its production and quality control under GMP-compliance. For this purpose, all analytical methods have to be validated. [18F]PSMA-1007 is easily radiosynthesized in a one-step procedure and isolated using solid phase extraction (SPE) cartridges followed by formulation of a buffered injection solution and for the determination of its chemical and radiochemical purity a robust, fast and reliable quality control method using radio-HPLC is necessary. After development and optimizations overcoming problems in reproducibility, the here described radio-HPLC method fulfills all acceptance criteria—for e.g., specificity, linearity, and accuracy—and is therefore well suited for the routine quality control of [18F]PSMA-1007 before release of the radiopharmaceutical. Recently a European Pharmacopeia monograph for [18F]PSMA-1007 was published suggesting a different radio-HPLC method for the determination of its chemical and radiochemical purity. Since the here described method has certain advantages, not least of all easier technical implementation, it can be an attractive alternative to the monograph method. The here described method was successfully validated on several radio-HPLC systems in our lab and used for the analysis of more than 60 batches of [18F]PSMA-1007. Using this method, the chemical and radiochemical purity of [18F]PSMA-1007 can routinely be evaluated assuring patient safety.

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although 61Cu and 64Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart 67Cu plays a key role for further radiopharmaceutical development in the future. Until now, the 67Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added 67Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the 70Zn(p,α)67Cu reaction. With this purpose, proton irradiation of electrodeposited 70Zn targets was performed followed by two-step radiochemical separation based on solid-phase extraction. Activities of up to 600MBq 67Cu at end of bombardment, with radionuclidic purities over 99.5% and apparent molar activities of up to 80MBq/nmol, were quantified.