Antimicrobial peptides (AMPs) are a heterogeneous class of compounds found in a variety of organisms including humans and, so far, hundreds of these structures have been isolated and characterised. They can be described as natural microbicide, selectively cytotoxic to bacteria, whilst showing minimal cytotoxicity towards the mammalian cells of the host organism. They act by their relatively strong electrostatic attraction to the negatively charged bacterial cells and a relatively weak interaction to the eukaryote host cells. The ability of these peptides to accumulate at sites of infection combined with the minimal host's cytotoxicity motivated for this review to highlight the role and the usefulness of AMPs for PET with emphasis on their mechanism of action and the different interactions with the bacterial cell. These details are key information for their selective properties. We also describe the strategy, design, and utilization of these peptides as potential radiopharmaceuticals as their combination with nuclear medicine modalities such as SPECT or PET would allow noninvasive whole-body examination for detection of occult infection causing, for example, fever of unknown origin.

PurposeThe prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate 161Tb (T1/2 = 6.89 days; Eβ-uperscript>av = 154 keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to 177Lu-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.Methods161Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100 MBq/nmol. 161Tb-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for 177Lu-PSMA-617. The effects of 161Tb-PSMA-617 and 177Lu-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. 161Tb-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.Results161Tb-PSMA-617 and 177Lu-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to 161Tb-PSMA-617 as compared to the effect obtained with the same activities of 177Lu-PSMA-617 over the whole investigated concentration range. Treatment of mice with 161Tb-PSMA-617 (5.0 MBq/mouse and 10 MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65 days) compared to untreated control animals (19 days). Therapy studies to compare the effects of 161Tb-PSMA-617 and 177Lu-PSMA-617 indicated the anticipated superiority of 161Tb over 177Lu.Conclusion161Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to 177Lu-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of 161Tb. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of 161Tb-PSMA-617 for the treatment of mCRPC.Electronic supplementary materialThe online version of this article (10.1007/s00259-019-04345-0) contains supplementary material, which is available to authorized users.

BackgroundTo report on imaging findings using 68Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.Methods 68Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.ResultsOut of 81 tumor lesions identified, 84% were identified on 68Ga-PSMA-HBED-CC PET. 68Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and 68Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015).Conclusions 68Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 ( 68 Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative 68 Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of 68 Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphaticand metastatic lesions. The 68 Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance.

Introduction: Human antimicrobial peptides are of interest for the development of positron

Background 161 Tb is an interesting radionuclide for cancer treatment, showing similar decay characteristics and chemical behavior to clinically-employed 177 Lu. The therapeutic effect of 161 Tb, however, may be enhanced due to the co-emission of a larger number of conversion and Auger electrons as compared to 177 Lu. The aim of this study was to produce 161 Tb from enriched 160 Gd targets in quantity and quality sufficient for first application in patients. Methods No-carrier-added 161 Tb was produced by neutron irradiation of enriched 160 Gd targets at nuclear research reactors. The 161 Tb purification method was developed with the use of cation exchange (Sykam resin) and extraction chromatography (LN3 resin), respectively. The resultant product ( 161 TbCl 3 ) was characterized and the 161 Tb purity compared with commercial 177 LuCl 3 . The purity of the final product ( 161 TbCl 3 ) was analyzed by means of γ-ray spectrometry (radionuclidic purity) and radio TLC (radiochemical purity). The radiolabeling yield of 161 Tb-DOTA was assessed over a two-week period post processing in order to observe the quality change of the obtained 161 Tb towards future clinical application. To understand how the possible drug products (peptides radiolabeled with 161 Tb) vary with time, stability of the clinically-applied somatostatin analogue DOTATOC, radiolabeled with 161 Tb, was investigated over a 24-h period. The radiolytic stability experiments were compared to those performed with 177 Lu-DOTATOC in order to investigate the possible influence of conversion and Auger electrons of 161 Tb on peptide disintegration. Results Irradiations of enriched 160 Gd targets yielded 6–20 GBq 161 Tb. The final product was obtained at an activity concentration of 11–21 MBq/μL with ≥99% radionuclidic and radiochemical purity. The DOTA chelator was radiolabeled with 161 Tb or 177 Lu at the molar activity deemed useful for clinical application, even at the two-week time point after end of chemical separation. DOTATOC, radiolabeled with either 161 Tb or 177 Lu, was stable over 24 h in the presence of a stabilizer. Conclusions In this study, it was shown that 161 Tb can be produced in hig...

Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. 99m Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with 68 Ga, and investigated in a rabbit infection model. Methods: 68 Ga was obtained from a 1.85-GBq 68 Ge/ 68 Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. 68 Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ( 68 Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 6 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oilinduced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue. Results: PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of 68 Ga-NOTA-UBI29-41 peaked at 3.8 6 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 6 5.2 %ID was recovered in total urine. 68 Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/ inflamed) were 2.9 6 0.93, 2.9 6 0.50, 3.5 6 0.86, and 3.8 6 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. Conclusion: 68 Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation.

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