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Background: (S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic radiofluorination step. This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[18F]FETrp from a corresponding enantiopure tosylate precursor. Results: Enantiomerically pure (S)- and (R)-FETrp references as well as tosylate precursors (S)- and (R)-3 were obtained from corresponding Na-Boc-(L and D)-tryptophan in 2 and 4 steps, respectively. Manual optimisation of the radiolabelling conditions resulted in > 90% radiochemical conversion with more than 99% enantiomeric purity. Based on these results, the (S)-[18F]FETrp radiosynthesis was fully automated on a SynChrom R&D EVOI module to produce the radiotracer in 55.2 ± 7.5% radiochemical yield, 99.9% radiochemical purity, 99.1 ± 0.5% enantiomeric excess, and molar activity of 53.2 ± 9.3 GBq/µmol (n = 3). Conclusions: To avoid racemisation and complicated purification processes, currently encountered for the radiosynthesis of (S)-[18F]FETrp, we report herein significant improvements, including a versatile synthesis of enantiomerically pure tosylate precursor and reference compound and a convenient one-pot two-step automated procedure for the radiosynthesis of (S)-[18F]FETrp. This optimised and robust production method could facilitate further investigations of this relevant PET radiotracer for imaging IDO1 activity. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the quantification performance of a 360° CZT camera for 177Lu-based treatment monitoring. Methods: Three phantoms with known 177Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data. Results: Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for 177Lu-PSMA patients in 2–3 times faster than the time taken for a conventional gamma camera. Conclusion: Quantification of whole-body 3D images of patients treated with 177Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis (PC) is a common outcome of epithelial ovarian carcinoma and is the leading cause of death for these patients. Tumor location, extent, peculiarities of the microenvironment, and the development of drug resistance are the main challenges that need to be addressed to improve therapeutic outcome. The development of new procedures such as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) have enabled locoregional delivery of chemotherapeutics, while the increasingly efficient design and development of advanced drug delivery micro and nanosystems are helping to promote tumor targeting and penetration and to reduce the side effects associated with systemic chemotherapy administration. The possibility of combining drug-loaded carriers with delivery via HIPEC and PIPAC represents a powerful tool to improve treatment efficacy, and this possibility has recently begun to be explored. This review will discuss the latest advances in the treatment of PC derived from ovarian cancer, with a focus on the potential of PIPAC and nanoparticles in terms of their application to develop new therapeutic strategies and future prospects. [ABSTRACT FROM AUTHOR]

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of proinflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, in vitro studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment. [ABSTRACT FROM AUTHOR]