An Automated and Putatively Versatile Approach for Labeling Peptides with Fluorine-18 Using the FastlabTM Synthesizer; Exemplified with Glu-the CO-Lys Pharmacophore

Background: Noninvasive molecular imaging using peptides and biomolecules labelled with positron emitters has become important for detection of cancer and other diseases with PET (positron emission tomography). The positron emitting radionuclide fluorine-18 is widely available in high yield from cyclotrons and has favorable decay (t1/2 109.7 min) and imaging properties. 18F-Labelling of biomolecules and peptides for use as radiotracers is customarily achieved in a two-step approach, which can be challenging to automate. 6-[18F]Fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP) is a versatile 18F-prosthetic group for this purpose, which can be rapidly be produced in an one-step approach on solid support. This work details an automated procedure on the cassette-based GE FASTlabTM platform for the labeling of a peptidomimetic, exemplified by the case of using the Glu-CO-Lys motif to produce [18F]DCFPyL, a ligand targeting the prostate specific membrane antigen (PSMA). Results: From fluorine-18 delivery a fully automated two-step radiosynthesis of [18F]DCFPyL was completed in 56 min with an overall end of synthesis yield as high as 37% using SPE purification on the GE FASTlabTM platform. Conclusions: Putatively, this radiolabeling methodology is inherently amenable to automation with a diverse set of synthesis modules, and it should generalize for production of a broad spectrum of biomolecule-based radiotracers for use in PET imaging.

A Comprehensive Updated Review on Magnetic Nanoparticles in Diagnostics

Magnetic nanoparticles (MNPs) have been studied for diagnostic purposes for decades. Their high surface-to-volume ratio, dispersibility, ability to interact with various molecules and superparamagnetic properties are at the core of what makes MNPs so promising. They have been applied in a multitude of areas in medicine, particularly Magnetic Resonance Imaging (MRI). Iron oxide nanoparticles (IONPs) are the most well-accepted based on their excellent superparamagnetic properties and low toxicity. Nevertheless, IONPs are facing many challenges that make their entry into the market difficult. To overcome these challenges, research has focused on developing MNPs with better safety profiles and enhanced magnetic properties. One particularly important strategy includes doping MNPs (particularly IONPs) with other metallic elements, such as cobalt (Co) and manganese (Mn), to reduce the iron (Fe) content released into the body resulting in the creation of multimodal nanoparticles with unique properties. Another approach includes the development of MNPs using other metals besides Fe, that possess great magnetic or other imaging properties. The future of this field seems to be the production of MNPs which can be used as multipurpose platforms that can combine different uses of MRI or different imaging techniques to design more effective and complete diagnostic tests.

On site production of [18F]PSMA-1007 using different [18F]fluoride activities: practical, technical and economical impact

Background Prostate-specific membrane antigen is overexpressed in prostate cancer and it is considered a good target for positron emission tomography/computed tomography imaging of primary cancer and recurrent/metastatic disease, as well as for radioligand therapy. Different PSMA-analogues labeled with [68Ga]gallium have been investigated, showing excellent imaging properties; however, only small amounts can be produced for each radiolabeling. Recently, a [18F]fluoride labeled PSMA-inhibitor, [18F]PSMA-1007, has been introduced, and it has ensured large-scale productions, overcoming this limitation of [68Ga]PSMAs. In this study, PSMA-1007 has been labeled with low (A), medium (B) and high (C) starting activities of [18F]fluoride, in order to verify if radiochemical yield, radiochemical purity and stability of [18F]PSMA-1007 were affected. These parameters have been measured in sixty-five consecutive batches. In addition, the estimation of [18F]PSMA-1007 production costs is provided. Results The radiochemical yield for low and medium activities of [18F]fluoride was 52%, while for the high one it decreased to 40%. The radiochemical purity was 99% for all three activities. [18F]PSMA-1007 did not show radiolysis up to 8 h after the end of synthesis, confirming that the radiopharmaceutical is stable and suitable to perform diagnostic studies in humans for a long period of time after the end of radiolabeling. Furthermore, radiochemical stability was demonstrated in fetal bovine serum at 4 °C and 37 °C for 120′. Conclusions A starting activity of [18F]fluoride of 90 GBq (B) seems to be the best option enabling a final amount of about of 50 GBq of [18F]PSMA-1007, which is promising as it allows to: (a) perform a large number of scans, and/or (b) supply the radiopharmaceutical to any peripheral diagnostic centers in need.

Research Progress in the Synthesis of Targeting Organelle Carbon Dots and Their Applications in Cancer Diagnosis and Treatment

With increasing knowledge about diseases at the histological, cytological to sub-organelle level, targeting organelle therapy has gradually been envisioned as an approach to overcome the shortcomings of poor specificity and multiple toxic side effects on tissues and cell-level treatments using the currently available therapy. Organelle carbon dots (CDs) are a class of functionalized CDs that can target organelles. CDs can be prepared by a “synchronous in situ synthesis method” and “asynchronous modification method.” The superior optical properties and good biocompatibility of CDs can be preserved, and they can be used as targeting particles to carry drugs into cells while reducing leakage during transport. Given the excellent organelle fluorescence imaging properties, targeting organelle CDs can be used to monitor the physiological metabolism of organelles and progression of human diseases, which will provide advanced understanding and accurate diagnosis and targeted treatment of cancers. This study reviews the methods used for preparation of targeting organelle CDs, mechanisms of accurate diagnosis and targeted treatment of cancer, as well as their application in the area of cancer diagnosis and treatment research. Finally, the current difficulties and prospects for targeting organelle CDs are prospected.

Optimizing the Performance of 68Ga Labeled FSHR Ligand in Prostate Cancer Model by Means of Aprotinin

Purpose: Radiolabeled FSH1 peptides are potential specific probes for FSHR imaging. However, moderate uptakes and fast washout from the tumors may limit its widespread use. In this study, 68Ga labeled modified FSH1 analogs was prepared and the imaging properties were determined in the prostate cancer model with or without aprotinin.Methods: NOTA-MAL-FSH4 was synthesized and labeled with 68Ga. The pharmacokinetic profile of the peptide after co-administration with aprotinin was determined through metabolism analyses and microPET imaging.Results: 68Ga-NOTA-MAL-FSH4 was successfully prepared. The IC50 value of displacement 68Ga-NOTA-MAL-FSH4 with FSH1 was 139.4±1.16 nM. The PC-3 prostate tumor was visible after administration of the 68Ga labeled tracer. In vitro RP-HPLC analysis revealed that the average percentage of intact peptide in the plasma, liver and tumor was 8.30, 9.57 and 7.06 % respectively. In presence of aprotinin, the amounts of intact peptide increased to 34.32%, 20.63 % and 15.39 % in the counterparts respectively. MicroPET imaging showed that the uptakes of PC-3 tumors at 60mins after co-administration of 100μg, 200μg or 400μg enzyme inhibitors were 2.91±0.21%ID/g, 3.89±0.16%ID/g and 9.21±0.22%ID/g respectively.Conclusion: With the aid of a serine protease inhibitor, the performance of the 68Ga labeled peptide was optimized, which may benefit further clinical application.

CT and MRI Imaging Characteristics of Gastrointestinal and Mesangial Reactive Nodular Fibrous Pseudotumor Based on Virtual Reality

In recent years, with the continued development and development of science and technology and the increasing maturity of medical technology, reactive nodular fibrous pseudotumors remain difficult to diagnose. Therefore, this paper studies CT and MRI imaging properties based on hypothetical gastrointestinal and mesangial reactive erythema nodosum fibrous pseudotumors to improve the diagnosis and treatment of reactive nodular fibrous pseudotumors. In this study, 48 patients with gastrointestinal and intermediate-reactive erythema nodosum fibrous pseudotumors in the gastrointestinal tract and experimental group were screened and identified by surgical pathology and immunohistochemistry. CT or magnetic resonance imaging was used in all patients. An analysis is performed, and the diagnostic values are compared with the pathological results. Experiments have proved that the postoperative reexamination of reactive nodular fibrous pseudotumors found that single masses are common, tumor sizes are different, and most small nodules have relatively more uniform lesion density, and the density of the plain scan is close to the muscle density, and the delay can be seen after enhancement. When the mass is large, the density is uniform, and low-density foci of different degrees can be seen in some masses, and this part rarely shows enhancement. The imaging phenomenon and clinical features of reactive nodular fibrous pseudotumors have specific features that distinguish them from invasive tumors such as gastrointestinal stromal tumors and provide an important basis for accurate clinical diagnosis and treatment.

Facile and Large-scale Synthesis of Graphene Quantum Dots Functionalized with Morpholine for Selective Targeting and Imaging of Lysosome

The lack of targeting selection to lysosome limits the application of graphene quantum dots (GQDs) in the diagnosis and treatment of lysosome-related disease. In this study, we developed a facile, environmentally friendly and large-scale method to prepare [Formula: see text]-aminomorpholine (Am)-modified GQDs (Am-GQDs) via a simple hydrothermal method. The physicochemical, optical, biocompatible and targeted imaging properties were evaluated systematically. The results indicated that the synthesized Am-GQDs had a uniform size distribution and the size was around 2[Formula: see text]nm. In addition, the synthesized Am-GQDs had excellent optical properties, fluorescent stability, and good biocompatibility. More importantly, they can selectively target and image lysosome in a relatively short coculture time with cells, demonstrating their application potential in the diagnosis and treatment of lysosomal-related diseases.

A Pure NanoICG-Based Homogeneous Lipiodol Formulation: Toward Precise Surgical Navigation of Hepatocellular Carcinoma After Long-Term Transcatheter Arterial Embolization

Purpose To surmount the critical issues of clinical hepatectomy and achieve a precise surgical navigation of hepatocellular carcinoma after long-term transcatheter arterial embolization (TAE).Methods A facile and green pure-nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG). The nanoICG was dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for TAE combined with near-infrared fluorescence-guided precise hepatectomy.Results We demonstrate that SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging properties, and specific tumoral deposition to recognize tumor regions, featuring sufficient physical stability for fluorescence-guided precise hepatectomy. Importantly, SHIFT nanoICG is capable of visualizing all lesions in rabbit-bearing VX2 orthotopic hepatocellular carcinoma models, even the tiny focus to 0.6 × 0.4 mm.Conclusion Our findings indicate that SHIFT nanoICG provides a promising avenue to address the clinical issue of hepatectomy and has excellent potential for a translational pipeline.

Metallodrugs as Anticancer Chemotherapeutics and Diagnostic Agents: A Critical Patent Review (2010-2020)

Background: The development of metallodrugs with potential applications in cancer treatment and diagnosis has been a hot topic since the approval and subsequent marketing of the anticancer drug cisplatin in 1978. Since then, thousands of metal-based derivatives have been reported and evaluated for their chemotherapeutic or tumor imaging properties, but only a very limited number gained clinical status. Nonetheless, research in the field has been increasing exponentially over the years, especially in a view to exploiting novel drug designing approaches and strategies aimed at improving pharmacological outcomes and, at the same time, reducing side-effects. Objective: This review article reports on the patents filed during the last decade and strictly focusing on the development of metal-based anticancer and diagnostic agents. The goal is to identify the latest trends and designing strategies in the field, which would represent a valuable starting point to researchers interested in the development of metallodrugs. Methods: The most relevant patents filed in the 2010-2020 timeframe have been retrieved from various databases using dedicated search engines (such as SciFinder, Google Patents, PatentPak, Espacenet, Global Dossier, PatentScope), sorted by type of metallodrug and screened to include those reporting a substantial amount of biological data. Results : The majority of patents here reviewed are concerned with metallodrugs (mostly platinum-based) showing interesting pharmacological properties but no specific tumor-targeting features. Nonetheless, some promising trends in the development of novel drug delivery strategies and/or metallodrugs with potential applications in targeted chemotherapy are envisaged. Conclusion: In this review, the latest trends in the development of metallodrugs from recent patents are summarized and critically discussed. Such trends would be of interest not only to the scientific community but also to lay audiences aiming to broaden their knowledge of the field and industrial stakeholders potentially interested in the exploitation and commercialization of this class of pharmaceuticals.