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.

Background: Alternative positron-emission tomography (PET) probes like labeled inhibitors of the prostate-specific membrane antigen (PSMA) are of emerging clinical impact as they show the ability to image small lesions of recurrent prostate cancer. Here, the dimerization of the pharmacophore Glu‐ureido‐Lys via the ⁶⁸Ga chelator N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) was investigated to further improve the binding characteristics and pharmacokinetics. Methods: The peptidomimetic structures were synthesized by solid-phase chemistry, and the resulting products were coupled with the respective 2,3,5,6-tetrafluorophenol esters of HBED-CC to form the monomeric reference and the dimeric Glu‐ureido‐Lys derivative. The binding properties were analyzed in competitive binding, internalization, and cell surface retention experiments. PET images and biodistribution data were obtained 1 h after injection in BALB/c nu/nu mice bearing LNCaP tumor xenografts. Results: Cell binding data revealed significant better binding properties of the dimer (IC₅₀ = 3.9 ± 1.8 nM; IC₅₀ (monomer) = 12.1 ± 2.1 nM). The inhibition potency investigated by the enzyme-based NAALADase assay confirmed these results. Specific internalization in LNCaP cells was demonstrated for both, the monomer and dimer. As shown by efflux measurements, the dimeric compound was more effectively retained on the cell surface, resulting in advanced in vivo properties (T/B_Monomer = 9.2; T/B_Dimer = 26.5). Conclusions: The dimeric [⁶⁸Ga]7 is a promising imaging agent for PSMA-expressing tumors as it shows higher tumor uptake while observing more favorable background clearance. As compared to the respective monomer, the higher affinity and prolonged tumor retention additionally represent promising features and warrant further evaluation regarding ⁶⁸Ga-PET imaging of PSMA expression.

Multidrug‐resistant bacteria represent one of the biggest challenges facing modern medicine. The increasing prevalence of glycopeptide resistance compromises the efficacy of vancomycin, for a long time considered as the last resort for the treatment of resistant bacteria. To reestablish its activity, polycationic peptides were conjugated to vancomycin. By site‐specific conjugation, derivatives that bear the peptide moiety at four different sites of the antibiotic were synthesized. The most potent compounds exhibited an approximately 1000‐fold increased antimicrobial activity and were able to overcome the most important types of vancomycin resistance. Additional blocking experiments using d‐Ala‐d‐Ala revealed a mode of action beyond inhibition of cell‐wall formation. The antimicrobial potential of the lead candidate FU002 for bacterial infection treatments could be demonstrated in an in vivo study. Molecular imaging and biodistribution studies revealed that conjugation engenders superior pharmacokinetics.

Despite the advances in molecular biology and biochemistry, the prognosis of patients suffering from tumor diseases remains poor. The limited therapeutic success can be explained by the insufficient performance of the common chemotherapeutic drugs that lack the ability to specifically target tumor tissues. Recently peptide radiopharmaceuticals have been developed that enable the concurrent imaging and therapy of tumors expressing a specific target. Here, with a special emphasis on the synthesis of the building blocks required for the complexation of metallic radioisotopes, the requirements to the design and synthesis of radiolabeled peptides for clinical applications are described.