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Two pretreatment method, including the normal activation and the ultrasonic agitation in acidic bath, were used during the pretreatment of AZ91D substrate, for which the electroless Ni-W-P coating was prepared. The microstructure, bonding strength and corrosion resistance were compared. The effect of different activation condition on the microstructure and corrosion resistance was investigated and discussed. Results demonstrate that ultrasonic agitation has negligible effect on the microstructure, chemical composition, but improves the bonding strength and corrosion resistance of Ni-W-P coating. The corrosion resistance of Ni-W-P coating via ultrasonic pretreatment was less dependent on the deposition time. Ultrasonic agitation facilitates the deposition of Ni on the β phase and the eutectic phase, and improves the compactness at Mg/Ni interface by decreasing the inclusion of MgF 2 , which are critical for improving the quality of Ni-W-P coating. • Ultrasonic agitation (UA) was applied on AZ91D to prepare Ni-W-P coating. • Chemical composition and structure were not affected by UA. • The corrosion resistance and bonding strength were improved by UA. • The corrosion resistance of coating by UA was independent on deposition time. • UA improves the corrosion resistance by removing the activation products. [ABSTRACT FROM AUTHOR]

An editorial is presented on predicting the status of PD-1 (programmed death protein 1) and its natural ligand PD-L1 in bladder cancer with F-FDG PET. Topics discussed include immunotherapy as a novel cancer treatment, and relationships between FBP1 expression and FDG uptake in hepatocellular carcinoma.

Abstract: The TRIS scaffold, Boc-β-Ala-TRIS-(OH)3, was utilized to assemble triple helices composed of the Gly-Nleu-Pro sequence (Nleu denotes N-isobutylglycine). The scaffold assembly can be achieved efficiently through direct coupling between long peptide chains and the TRIS scaffold using DEPBT, a recently developed peptide coupling reagent. CD spectroscopy and thermal denaturation studies demonstrated that Boc-β-Ala-TRIS-[(Gly-Nleu-Pro) n -OMe]3 exhibits triple helicity in H2O when n equals 5, 6, and 8, while the shorter analogs (where n =1 and 4) do not. TRIS-assembled structures possess several advantages over the KTA- and TREN-assembled structures previously reported from our laboratory (where KTA and TREN denotes cis-1,3,5-trimethyl cyclohexane-1,3,5-tricarboxylic acid and tris(2-aminoethyl)amine, respectively). The protecting groups on the scaffold and at the C-terminus of the TRIS-assembled peptides can be readily removed to synthesize collagen mimetic dendrimers and metal-complexing collagen-like peptides respectively, both of which can lead to further enhanced thermal stability. [Copyright &y& Elsevier]

Single-walled carbon nanotubes (SWNTs) exhibit unique size, shape and physical properties that make them promising candidates for biological applications. Here, we investigate the biodistribution of radio-labelled SWNTs in mice by in vivo positron emission tomography (PET), ex vivo biodistribution and Raman spectroscopy. It is found that SWNTs that are functionalized with phospholipids bearing polyethylene-glycol (PEG) are surprisingly stable in vivo. The effect of PEG chain length on the biodistribution and circulation of the SWNTs is studied. Effectively PEGylated SWNTs exhibit relatively long blood circulation times and low uptake by the reticuloendothelial system (RES). Efficient targeting of integrin positive tumour in mice is achieved with SWNTs coated with PEG chains linked to an arginine–glycine–aspartic acid (RGD) peptide. A high tumour accumulation is attributed to the multivalent effect of the SWNTs. The Raman signatures of SWNTs are used to directly probe the presence of nanotubes in mice tissues and confirm the radio-label-based results. [ABSTRACT FROM AUTHOR]

Abstract: Up-regulation of integrin αvβ3 has been shown to play a key role in tumor angiogenesis and metastasis. In this study, we evaluated the role of integrin αvβ3 in breast cancer cell resistance to ionizing irradiation (IR) and tested the anti-tumor efficacy of combining integrin αv siRNA and IR. Colonogenic survival assay, cell proliferation, apoptosis, and cell cycle analysis were carried out to determine the treatment effect of siRNA, IR, or combination of both on MDA-MB-435 cells (integrin αvβ3-positive). Integrin αvβ3-negative MCF-7 cells exert more radiosensitivity than MDA-MB-435 cells. IR up-regulates integrin αvβ3 expression in MDA-MB-435 cells and integrin αv siRNA can effectively reduce both αv and αvβ3 integrin expression, leading to increased radiosensitivity. Integrin αv siRNA also promotes IR-induced apoptosis and enhances IR-induced G2/M arrest in cell cycle progression. This study, with further optimization, may provide a simple and highly efficient treatment strategy for breast cancer as well as other integrin αvβ3-positive cancer types. [Copyright &y& Elsevier]

We report the in vivo targeting and imaging of tumor vasculature using arginine-glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD intravenously. The tumor fluorescence intensity reached maximum at 6 h postinjection with good contrast. The results reported here open up new perspectives for integrin-targeted near-infrared optical imaging and may aid in cancer detection and management including imaging-guided surgery. [ABSTRACT FROM AUTHOR]

A recent article in the European Journal of Nuclear Medicine & Molecular Imaging discusses the development of a macrocyclic peptide PET radioligand for PD-L1, a protein involved in immune checkpoint mechanisms. The article highlights the challenges and opportunities in individualizing treatment for patients who could benefit from anti-PD-1/PD-L1 therapy and monitoring their response during therapy. The authors present a study on the discovery and evaluation of a novel fluorine-18 labeled macrocyclic peptide-based PET ligand, [18F]BMS-986229, which demonstrated high affinity for PD-L1 and rapid clearance from non-PD-L1 tissues. The study suggests that this ligand has the potential to facilitate a broader clinical application of PD-L1 PET imaging. [Extracted from the article]

The article discusses the use of positron emission tomography (PET) imaging for the visualization and quantification of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in cancer treatment. The development of small molecule radiotracers for PET imaging of PD-L1 is explored as an alternative to radiolabeled antibodies, with advantages including rapid clearance and improved tissue penetration. Various small molecule tracers, such as WL12, PEG-TPP-1, nanobodies, and D-peptides, are discussed, highlighting their potential for PET imaging of PD-L1 expression in tumors. The article also introduces a novel small-molecule radiotracer called [68Ga]Ga-D-PMED, which shows promise for visualizing PD-L1 expression in vivo. Comparative studies of different tracers can provide insights into their strengths and limitations, aiding in the development of improved PET imaging strategies for personalized immunotherapy in cancer patients. [Extracted from the article]

This article discusses the use of radiomics, a method that involves extracting imaging features from radiologic images, to predict lymph node metastasis (LNM) in colorectal cancer (CRC) patients. The study found that radiomics analysis using 2-[18F]FDG PET-based imaging was more effective in predicting LNM compared to traditional CT and PET reports. The study also highlighted the need for standardization in radiomics workflow and the development of automated segmentation tools. While promising, further research and validation in larger clinical trials are needed before radiomics can be integrated into routine clinical practice. [Extracted from the article]

Purpose: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. Methods: 169Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. Results: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. Conclusions: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers. [ABSTRACT FROM AUTHOR]

A combination of [ SP 18 sp F]-FBY PET with various other imaging techniques or other PET tracers that can better delineate early-stage, low-grade brain tumors may be needed for the sub-population of low-grade cancer patients, since early and accurate detection of brain tumor is crucial for longer survival and better clinical outcome. 1a), were developed and readily labeled with SP 18 sp F for PET imaging, which can serve as general imaging probes for AATs [[24]]. This article is part of the Topical Collection on Radiopharmacy Given the many limitations of [ SP 18 sp F]-FDG in glioma imaging, such as high background uptake in normal brain tissue and significant uptake in inflammation, the quest for better positron emission tomography (PET) tracers for brain tumor imaging has been constant [[1]]. [Extracted from the article]

The therapeutic efficacy of photodynamic therapy is limited by the ability of light to penetrate tissues. Due to this limitation, Cerenkov luminescence (CL) from radionuclides has recently been proposed as an alternative light source in a strategy referred to as Cerenkov radiation‐induced therapy (CRIT). Semiconducting polymer nanoparticles (SPNs) have ideal optical properties, such as large absorption cross‐sections and broad absorbance, which can be utilized to harness the relatively weak CL produced by radionuclides. SPNs can be doped with photosensitizers and have ≈100% energy transfer efficiency by multiple energy transfer mechanisms. Herein, an optimized photosensitizer‐doped SPN is investigated as a nanosystem to harness and amplify CL for cancer theranostics. It is found that semiconducting polymers significantly amplify CL energy transfer efficiency. Bimodal positron emission tomography (PET) and optical imaging studies show high tumor uptake and retention of the optimized SPNs when administered intravenously or intratumorally. Lastly, it is found that photosensitizer‐doped SPNs have excellent potential as a cancer theranostics nanosystem in an in vivo tumor therapy study. This study shows that SPNs are ideally suited to harness and amplify CL for cancer theranostics, which may provide a significant advancement for CRIT that are unabated by tissue penetration limits. [ABSTRACT FROM AUTHOR]

In this study, radiolabeled FAPI-46-F1D (IC SB 50 sb = 157.8 ± 14.5 pM) and FAPI-46-Ibu (IC SB 50 sb = 39.4 ± 16.1 pM) showed enhanced inhibitory activity, while FAPI-46-EB (IC SB 50 sb = 634.3 ± 102.3 pM) and FAP-2286 (IC SB 50 sb = 247.6 ± 71.1 pM) showed reduced or very similar inhibitory activity compared to FAPI-46 (IC SB 50 sb = 247.0 ± 17 pM). The first approach is multimerization of high-affinity FAPI ligands to enhance residence time in FAP-positive tumors [[10]], such as dimeric FAPI ligands that offer better chances of rebinding to their target, with slower off-rates than are seen with their monovalent counterparts [[9]-[11]]. While the potential of these radiolabeled FAPIs as SPECT/PET imaging agents is incontestable, their suitability for therapy is impaired by their short tumor retention leading to suboptimal radiation doses to the tumor [[2], [8]]. [Extracted from the article]

Positron emission tomography (PET) provides quantitative information in vivo with ultra‐high sensitivity but is limited by its relatively low spatial resolution. Therefore, PET has been combined with other imaging modalities, and commercial systems such as PET/computed tomography (CT) and PET/magnetic resonance (MR) have become available. Inspired by the emerging field of nanomedicine, many PET‐based multimodality nanoparticle imaging agents have been developed in recent years. This Minireview highlights recent progress in the design of PET‐based multimodality imaging nanoprobes with an aim to overview the major advances and key challenges in this field and substantially improve our knowledge of this fertile research area. Recent developments in multimodality imaging nanoprobes are systemically discussed in this Minireview, with a focus on the design of PET‐based dual‐ and higher‐modality imaging agents and their properties, biomedical applications, and significant clinical prospects. [ABSTRACT FROM AUTHOR]

Positronenemissionstomographie (PET) liefert quantitative In‐vivo‐Informationen mit höchster Empfindlichkeit, ist aber von einer vergleichsweise niedrigen räumlichen Auflösung geprägt. Um diese Einschränkung zu überwinden, stehen kommerziell erhältliche Kombinationen aus PET und orthogonalen Bildgebungsverfahren zur Verfügung, wie etwa PET/Computertomographie (CT) oder PET/Magnetresonanztomographie (MR). Inspiriert von Entwicklungen in der Nanomedizin sind zahlreiche Nanopartikel zur Kontrastverstärkung multimodaler Bildgebungsverfahren entwickelt worden. Dieser Kurzaufsatz fasst die jüngsten Entwicklungen bei PET‐basierten Nanosonden zusammen und gibt einen Überblick über die wichtigsten Fortschritte und Herausforderungen in diesem Gebiet. Multimodale Nanosonden werden in diesem Kurzaufsatz diskutiert, mit besonderem Schwerpunkt auf der Entwicklung PET‐basierter dualer und multimodaler Kontrastmittel. Eigenschaften, biomedizinische Anwendungen und Perspektiven für den klinischen Einsatz werden beschrieben. [ABSTRACT FROM AUTHOR]

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery. [ABSTRACT FROM AUTHOR]

The article presents information on the metal-assisted assembly and stabilization of collagen-like triple helices. The primary sequence of triple helical collagen is composed of Gly-Xaa-Yaa trimer repeats. A variety of scaffolds have been utilized to facilitate the assembly of collagen-like triple helices. Two possibilities exist. If the Fe3+-catechol complex is intermolecular, the resulting structure, as well as the stabilization effect, would be similar to that of the collagen mimetic dendrimer reported earlier (where three TRIS-assembled structures were attached to a trimesic acid core structure via the β-Ala linker).

Reports on the synthesis and conformational properties of 162-residue collagen mimetic dendrimers which exhibit enhanced triple helical stability compared to equivalent scaffold terminated structures. Utilization of a scaffold to assemble collagen mimetics; Determination of the triple helicity of all structures.

Incorporation of ABDs into nanobodies will enable the fusion proteins simultaneously binding to endogenous albumin, thereby extending their cycle time and increasing tumor uptake, leading to improved imaging contrast [[21]]. SP 177 sp Lu-MIRC213-709 has demonstrated excellent tumor uptake and prolonged blood circulation time, with a tumor uptake of 6.59 ± 1.67, 27.65 ± 7.66, 30.82 ± 7.29, 19.95 ± 1.76, and 17.61 ± 2.63 %ID/g at 1, 24, 48, 72, and 120 h post-injection, respectively ( I n i = 4). Another promising strategy involves fusing nanobodies with an albumin-binding domain (ABD) to extend their cycle time and increase tumor uptake, leading to improved imaging contrast [[16]]. [Extracted from the article]

Lung cancer has been the leading cause of cancer-related deaths worldwide for decades. Despite the increasing understanding of the underlying disease mechanisms, the prognosis still remains poor for many patients. Novel adjuvant therapies have emerged as a promising treatment method to augment conventional methods and boost the therapeutic effects of primary therapies. Adjuvant therapy based on nanomedicine has gained considerable interest for supporting and enhancing traditional therapies, such as chemotherapy, immunotherapy, and radiotherapy, due to the tunable physicochemical features and ease of synthetic design of nanomaterials. In addition, nanomedicine can provide protective effects against other therapies by reducing adverse side effects through precise disease targeting. Therefore, nanomedicine-based adjuvant therapies have been extensively employed in a wide range of preclinical and clinical cancer treatments to overcome the drawbacks of conventional therapies. In this review, we mainly discuss the recent advances in adjuvant nanomedicine for lung cancer treatment and highlight their functions in improving the therapeutic outcome of other therapies, which may inspire new ideas for advanced lung cancer therapies and stimulate research efforts around this topic. [ABSTRACT FROM AUTHOR]

Purpose: This review aims to provide a comprehensive overview of the latest literature on personalized lung cancer management using different ligands and radionuclide-based tumor-targeting agents. Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the heterogeneity of lung cancer, advances in precision medicine may enhance the disease management landscape. More recently, theranostics using the same molecule labeled with two different radionuclides for imaging and treatment has emerged as a promising strategy for systemic cancer management. In radionuclide-based theranostics, the target, ligand, and radionuclide should all be carefully considered to achieve an accurate diagnosis and optimal therapeutic effects for lung cancer. Methods: We summarize the latest radiotracers and radioligand therapeutic agents used in diagnosing and treating lung cancer. In addition, we discuss the potential clinical applications and limitations associated with target-dependent radiotracers as well as therapeutic radionuclides. Finally, we provide our views on the perspectives for future development in this field. Conclusions: Radionuclide-based theranostics show great potential in tailored medical care. We expect that this review can provide an understanding of the latest advances in radionuclide therapy for lung cancer and promote the application of radioligand theranostics in personalized medicine. [ABSTRACT FROM AUTHOR]

PSMA theranostics: review of the current status of PSMA-targeted imaging and radioligand therapy. Astatine-211 for PSMA-targeted -radiation therapy of micrometastatic prostate cancer: a sustainable approach towards precision oncology Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging. Several peptidomimetic inhibitors of PSMA (such as PSMA-11, PSMA-617, PSMA I&T, MIP-1095, DCFPyL, etc.) typically having a Glu-ureido component that serves as the PSMA binding motif have been designed and translated for routine clinical use [[4], [7]-[9]]. [Extracted from the article]

The article focuses on bispecific proteins, particularly bispecific antibodies (BsAbs), and their potential in the treatment of diseases. Topics covered include the advantages and classifications of BsAbs, their application in pancreatic ductal adenocarcinoma (PDAC) treatment using an ultra-small bispecific fusion protein, and the use of bispecific proteins in nuclear medicine for imaging and combination therapies.

Purpose: Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using Cu-labeled pertuzumab for immunoPET imaging. Methods: HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of Cu-NOTA-pertuzumab. Results: HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. Cu-NOTA-pertuzumab showed high specificity for HER2 (K = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively ( n = 3). In orthotopic models, PET imaging with Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer. Conclusions: Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification. [ABSTRACT FROM AUTHOR]

The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials. [ABSTRACT FROM AUTHOR]

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. [ABSTRACT FROM AUTHOR]

Besides being the carrier of genetic information, DNA is also an excellent biological organizer to establish well-designed nanostructures in the fields of material engineering, nanotechnology, and biomedicine. DNA-based materials represent a diverse nanoscale system primarily due to their predictable base pairing and highly regulated conformations, which greatly facilitate the construction of DNA nanostructures with distinct shapes and sizes. Integrating the emerging advancements in bioconjugation techniques, DNA nanostructures can be readily functionalized with high precision for many purposes ranging from biosensors to imaging to drug delivery. Recent progress in the field of DNA nanotechnology has exhibited collective efforts to employ DNA nanostructures as smart imaging agents or delivery platforms within living organisms. Despite significant improvements in the development of DNA nanostructures, there is limited knowledge regarding the in vivo biological fate of these intriguing nanomaterials. In this review, we summarize the current strategies for designing and purifying highly-versatile DNA nanostructures for biological applications, including molecular imaging and drug delivery. Since DNA nanostructures may elicit an immune response in vivo , we also present a short discussion of their potential toxicities in biomedical applications. Lastly, we discuss future perspectives and potential challenges that may limit the effective preclinical and clinical employment of DNA nanostructures. Due to their unique properties, we predict that DNA nanomaterials will make excellent agents for effective diagnostic imaging and drug delivery, improving patient outcome in cancer and other related diseases in the near future. [ABSTRACT FROM AUTHOR]

An editorial is presented on use of Photodynamic therapy (PDT), a two-step process that utilizes light energy to excite a photosensitizer to generate harmful singlet oxygen, as an effective treatment approach for several types of cancer. It presents the views on comparison of PDT with conventional cancer treatments, such as chemotherapy and surgery.

Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body. Positron emission tomography and optical imaging demonstrated enhanced tumor accumulation of the polymer carriers in 4T1-bearing mice with increased tumor-to-blood and tumor-to-muscle ratios. Additionally, there was a significant accumulation of doxorubicin bound to various polymer carriers in EL4 tumors, as well as excellent in vivo therapeutic activity in EL4 lymphoma and moderate efficacy in 4T1 breast carcinoma. The linear nanomedicine showed at least comparable pharmacologic properties to the star-like nanomedicines regarding doxorubicin transport. Therefore, if multiple parameters are considered such as its optimized structure and simple and reproducible synthesis, this polymer carrier system is the most promising for further preclinical and clinical investigations. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality rates. In many non-prostate solid tumors such as HCC, prostate-specific membrane antigens (PSMA) are overexpressed in tumor-associated endothelial cells. Therefore, the aim of this study was to evaluate the performance of [68Ga]Ga-PSMA-617 PET imaging on HCC with different animal models, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX), and to explore its mechanisms of function. Methods: [68Ga]Ga-PSMA-617 was prepared. The expression level of PSMA in two human hepatocellular cancer cells (HepG2 and HuH-7) was evaluated, and the cellular uptakes of [68Ga]Ga-PSMA-617 were assayed. HepG2 and HuH-7 subcutaneous xenograft models, HepG2 orthotopic xenograft models, and four different groups of PDX models were prepared. Preclinical pharmacokinetics and performance of [68Ga]Ga-PSMA-617 were evaluated in different types of HCC xenografts models using small animal PET and biodistribution studies. Results: Low PSMA expression level of HepG2 and HuH-7 cells was observed, and the cellular uptake and blocking study confirmed the non-specificity of the PSMA-targeted probe binding to HepG2 and HuH-7 cells. In the subcutaneous xenograft models, the tumor uptakes at 0.5 h were 0.76 ± 0.12%ID/g (HepG2 tumors) and 0.78 ± 0.08%ID/g (HuH-7 tumors), respectively, which were significantly higher than those of the blocking groups (0.23 ± 0.04%ID/g and 0.20 ± 0.04%ID/g, respectively). In the orthotopic xenograft models, PET images clearly displayed the tumor locations based on the preferential accumulation of [68Ga]Ga-PSMA-617 in tumor tissue versus normal liver tissue, suggesting the possibility of using [68Ga]Ga-PSMA-617 PET imaging to detect primary HCC lesions in deep tissue. In the four different groups of HCC PDX models, PET imaging with [68Ga]Ga-PSMA-617 provided clear tumor uptakes with prominent tumor-to-background contrast, further demonstrating its potential for the clinical imaging of PSMA-positive HCC lesions. The staining of tumor tissue sections with CD31- and PSMA-specific antibodies visualized the tumor-associated blood vessels and PSMA expression on endothelial cells in subcutaneous, orthotopic tissues, and PDX tissues, confirming the imaging with [68Ga]Ga-PSMA-617 might be mediated by targeting tumor associated endothelium. Conclusion: In this study, in vivo PET on different types of HCC xenograft models illustrated high uptake within tumors, which confirmed that [68Ga]Ga-PSMA-617 PET may be a promising imaging modality for HCC by targeting tumor associated endothelium. [ABSTRACT FROM AUTHOR]

Despite the rapid development of immunotherapy, low response rates, poor therapeutic outcomes, and severe side effects still limit its implementation, making the augmentation of immunotherapy an important goal for current research. DNA, which is principally recognized for its functions of encoding genetic information, has recently attracted research interest due to its emerging role in immune modulation. Inspired by the intrinsic DNA‐sensing signaling that triggers the host defense in response to foreign DNA, DNA or nucleic acid‐based immune stimulators have been used in the prevention and treatment of various diseases. Besides that, DNA vaccines allow the synthesis of target proteins in host cells, subsequently inducing recognition of these antigens to provoke immune responses. On this basis, researchers have designed numerous vehicles for DNA and nucleic acid delivery to regulate immune systems. Additionally, DNA nanostructures are also implemented as vaccine delivery systems to elicit strong immune responses against pathogens and diseased cells. This review will introduce the mechanism of harnessing DNA‐mediated immunity for the prevention and treatment of diseases, summarize recent progress, and envisage their future applications and challenges. [ABSTRACT FROM AUTHOR]

In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a "chemical factory" including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well‐fitness of nanomaterials for disease and satisfactory therapeutic effect. [ABSTRACT FROM AUTHOR]

Personalized treatment plans for cancer therapy have been at the forefront of oncology research for many years. With the advent of many novel nanoplatforms, this goal is closer to realization today than ever before. Inorganic nanoparticles hold immense potential in the field of nano‐oncology, but have considerable toxicity concerns that have limited their translation to date. In this review, an overview of emerging biologically safe inorganic nanoplatforms is provided, along with considerations of the challenges that need to be overcome for cancer theranostics with inorganic nanoparticles to become a reality. The clinical and preclinical studies of both biodegradable and renal clearable inorganic nanoparticles are discussed, along with their implications. [ABSTRACT FROM AUTHOR]

Amino acid-based tracers have been extensively investigated for positron emission tomography (PET) imaging of brain tumors, and 11C-methionine (11C-MET) is one of the most extensively investigated. However, widespread clinical use of 11C-MET is challenging due to the short half-life of 11C and low radiolabeling yield. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yang and colleagues report an 18F-labeled boron-derived methionine analog, 18F-B-MET, as a potential substitute for 11C-MET in PET imaging of glioma. The push-button synthesis, highly efficient radiolabeling, and good imaging performance in glioma models make this tracer a promising candidate for future clinical translation. [ABSTRACT FROM AUTHOR]

An editorial is presented on announcing the publication of a European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI). Topics include indicated the ever-increasing global impact and infuence of EJNMMI in the feld of nuclear medicine and molecular imaging; and high-quality manuscripts on any specific focusing topic such as artifcial intelligence, new tracers, fibroblast activation protein inhibitor (FAPI), immunotherapy, and total-body PET.

Fibroblast activation protein (FAP) is a type II membrane-bound glycoprotein which is overexpressed in cancer-associated fibroblasts and activated fibroblasts at wound healing/inflammatory sites. Since the first clinical application of quinoline-based FAP ligands in 2018, FAP inhibitor (FAPI)-based PET imaging and radiotherapy have been investigated for a wide variety of diseases, both cancerous and non-cancerous. As a consequence, promising strides have been made in particular to improve the understanding of FAPI-based PET imaging and the potential value of FAPI-based tumor radiotherapy. Herein, we present a comprehensive review of radiolabeled FAPI, including their clinical translation, in order to clarify the current and potential future role of this class of molecules in nuclear medicine. In particular, this review underlines the value of FAPI radiopharmaceuticals in the diagnosis or therapy of tumors or benign conditions. However, limitations in present studies have hampered a precise evaluation of FAPI radiopharmaceuticals. Despite this, it will likely be worthwhile to further explore the clinical value of FAPI in diagnosis and therapy through better-designed and larger-population clinical trials in the future. [ABSTRACT FROM AUTHOR]

Catalytic radiosensitization opens up a new promising direction of radiotherapy enhancement from the perspective of catalytic chemistry, and also provides more opportunities for the design and application of biomedical catalytic materials. This review summarizes the ingenious design and application of catalytic nanomaterials in tumor catalytic radiosensitization from the aspects of electron modulation and energy conversion, respectively, and proposes the strategies, challenges and guidelines for the further development of the catalytic radiosensitization. [Display omitted] Radiotherapy is indispensable in clinical cancer treatment, but because both tumor and normal tissues have similar sensitivity to X-rays, their clinical curative effect is intrinsically limited. Advanced nanomaterials and nanotechnologies have been developed for radiotherapy sensitization, typically employing high atomic number (high-Z) materials to enhance the energy deposition of X-rays in tumor tissues, but the efficiency is largely limited by the toxicity of heavy metals. A new and promising approach for radiosensitization is catalytic radiosensitization, which takes advantage of the catalytic activity of nanomaterials triggered by radiation. The efficiency of catalytic radiosensitization can be greatly enhanced by electron modulation and energy conversion of nanocatalysts upon X-ray irradiation, further enhancing the clinical curative effect. In this review, we highlight the challenges and opportunities in cancer radiosensitization, discuss novel approaches to catalytic radiosensitization, and finally describe the development of catalytic radiosensitization based on an in-depth understanding of radio-nano interactions and catalysis–biological interactions. [ABSTRACT FROM AUTHOR]

Purpose: Abnormal CD38 expression in some hematologic malignancies, including lymphoma, has made it a biomarker for targeted therapies. Daratumumab (Dara) is the first FDA-approved CD38-specific monoclonal antibody, enabling successfully immunoPET imaging over the past years. Radiolabeled Dara however has a long blood circulation and delayed tumor uptake which can limit its applications. The focus of this study is to develop 64Cu-labeled Dara-F(ab′)2 for the visualization of CD38 in lymphoma models. Methods: F(ab′)2 fragment was prepared from Dara using an IdeS enzyme and purified with Protein A beads. Western blotting, flow cytometry, and surface plasmon resonance (SPR) were performed for in vitro assay. Probes were labeled with 64Cu after the chelation of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Small animal PET imaging and quantitative analysis were performed after injection of 64Cu-labeled Dara-F(ab′)2, IgG-F(ab′)2, and Dara for evaluation in lymphoma models. Results: Flow cytometry and SPR assay proved the specific binding ability of Dara-F(ab′)2 and NOTA-Dara-F(ab′)2 in vitro. Radiolabeling yield of [64Cu]Cu-NOTA-Dara-F(ab′)2 was over 90% and with a specific activity of 4.0 ± 0.6 × 103 MBq/μmol (n = 5). PET imaging showed [64Cu]Cu-NOTA-Dara-F(ab′)2 had a rapid and high tumor uptake as early as 2 h (6.9 ± 1.2%ID/g) and peaked (9.5 ± 0.7%ID/g) at 12 h, whereas [64Cu]Cu-NOTA-Dara reached its tumor uptake peaked at 48 h (8.3 ± 1.4%ID/g, n = 4). In comparison, IgG-F(ab′)2 and HBL-1 control groups found no noticeable tumor uptake. [64Cu]Cu-NOTA-Dara-F(ab′)2 had significantly lower uptake in blood pool, bone, and muscle than [64Cu]Cu-NOTA-Dara and its tumor-to-blood and tumor-to-muscle ratios were significantly higher than controls. Conclusions: [64Cu]Cu-NOTA-Dara-F(ab′)2 showed a rapid and high tumor uptake in CD38-positive lymphoma models with favorable imaging contrast, showing its promise as a potential PET imaging agent for future clinical applications. [ABSTRACT FROM AUTHOR]

Purpose: Without a standard test for pancreatic carcinomas, this highly lethal disease is normally diagnosed at its advanced stage, leading to a low survival rate of patients. Trophoblast cell-surface antigen 2 (Trop-2), a transmembrane glycoprotein, is associated with cell proliferation and highly expressed in most of solid epithelial tumors, including pancreatic cancer. A non-invasive method of imaging Trop-2 would greatly benefit clinical diagnosis and monitoring of pancreatic cancer. In the current study, 89Zr-labeled anti-Trop-2 antibody (AF650) was recruited for the systemic evaluation of Trop-2 as an immunoPET target for pancreatic cancer imaging. Methods: AF650 was conjugated with desferrioxamine (DFO) and then radiolabeled with 89Zr. Trop-2 expression levels were determined in three pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and AsPC-1) via western blot, flow cytometry, saturation binding assay, and immunofluorescence staining. The targeting capacity of 89Zr-DFO-AF650 was evaluated in mouse models with subcutaneous xenograft of pancreatic cancers via PET imaging and bio-distribution studies. In addition, a Trop-2-positive orthotopic cancer model was recruited for further validating the targeting specificity of 89Zr-DFO-AF650. Results: BxPC-3 cells expressed high levels of Trop-2, while AsPC-1 and MIA PaCa-2 cells expressed low levels of Trop-2. Additionally, 89Zr-DFO-AF650 exhibited high specificity to Trop-2 in BxPC-3 cells (Kd = 22.34 ± 2.509 nM). In subcutaneous xenograft models, about 28.8 ± 7.63%ID/g tracer accumulated in the BxPC-3 tumors at 120 h post injection, which was much higher than those reaching MIA PaCa-2 (6.76 ± 2.08%ID/g) and AsPC-1 (3.51 ± 0.69%ID/g) tumors (n = 4). More importantly, 89Zr-DFO-AF650 could efficiently distinguish primary tumors in the orthotopic BxPC-3 cancer model, showing high correlation between PET imaging and bio-distribution and sensitivity. Conclusions: 89Zr-DFO-AF650 can be effectively used to detect pancreatic cancer via Trop-2-mediated immunoPET in vivo, clearly revealing the great potential of Trop-2-based non-invasive imaging in pancreatic cancer detection and treatment monitoring. [ABSTRACT FROM AUTHOR]

With many desirable properties, nanoparticles hold tremendous potential for in vivo molecular imaging and improving the efficacy of small-molecule drugs. The pharmacokinetics (PK) and tissue distribution of nanoparticles largely define their in vivo performance and potential toxicity, which are fundamental issues that need to be elucidated. In this review article, we summarized how molecular imaging techniques (e.g., positron emission tomography, fluorescence imaging, etc.) can facilitate the investigation of PK profiles of nanoparticles using carbon nanotubes (CNTs) and quantum dots (QDs) as representative examples. Different imaging techniques can provide useful insights in monitoring the in vivo behavior and tissue distribution of these nanoparticles, and a number of strategies were utilized to optimize the PK profiles of CNTs and QDs. Based on the available literature reports, it can be concluded that chemical/physical properties of the nanoparticles (e.g., surface functionalization, hydrodynamic size, shape, surface charge, etc.), along with the administration routes/doses, can play critical roles in determining the PK and biodistribution pattern of nanoparticles. Robust chemistry for surface modification of nanoparticles is a prerequisite for successful future biomedical/clinical applications. [ABSTRACT FROM AUTHOR]

Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer. The scanner has a 194 cm axial field-of-view for PET imaging provided by > 500,000 detector elements, as well as an 80-row, 160-slice CT scanner for anatomical imaging and PET attenuation correction [[3]], and was later called the uEXPLORER PET/CT scanner (United Imaging Healthcare Co., Ltd.). This CT scan was used for attenuation coefficient (AC) instead of disease diagnosis, with its effective radiation dose (~ 2.4 mSv) being significantly lower than a typical diagnostic body CT exam and the CT component of a typical modern PET/CT exam (~ 5-10 mSv) [[13]-[15]]. [Extracted from the article]

Background: Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. Experimental: We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. Results: In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response. Conclusion: These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response. [ABSTRACT FROM AUTHOR]

With continued development and optimization of the PET/CT scanner, as well as cost reduction, we believe LAFOV PET/CT scanners will become widely available in the future, just like PET/CT scanners have replaced PET scanners more than a decade ago [[41]]. Although the CT dose was not specifically stated, the effective radiation dose associated with this type of low-dose CT scan is approximately 2-3 mSv, which is significantly lower than a typical diagnostic body CT exam and the CT component of a typical modern PET/CT exam (~ 5-10 mSv) [[21]-[23]]. With the constant advancements of CT tube and detector technologies [[24]], as well as artificial intelligence (AI)-based CT dose reduction technologies (e.g., TrueFidelity Deep Learning Image Reconstruction from GE Healthcare [[25]] and Advanced Intelligent Clear-IQ Engine from Canon Medical Systems USA Inc. [[27]-[29]]), it is very likely that the CT component of LAFOV PET/CT exam will be further reduced to the sub-mSv level in the near future, which means the entire whole-body PET/CT exam with a low dose of injected PET tracer can be achieved below 2 mSv. 10.1007/s00259-021-05357-5. 33866409 20 Tan H, Sui X, Yin H, Yu H, Gu Y, Chen S. Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer. [Extracted from the article]

The article discusses research which evaluated the in vivo pharmacokinetics and dosimetry of PEGylated liposomes for diagnostic and radiotherapeutic applications in neuroendocrine H727 tumor xenografts. Topics covered include the remote loading of radioisotopes into the liposomes, the internal radiotherapy applications of the liposomes as well as their potential normal tissue toxicity, and the therapeutic efficacy of Lu-liposomes.

Abstract: Nitric oxide (NO) and NO synthases (NOSs) are crucial factors in many pathophysiological processes such as inflammation, vascular/neurological function, and many types of cancer. Noninvasive imaging of NO or NOS can provide new insights in understanding these diseases and facilitate the development of novel therapeutic strategies. In this review, we will summarize the current state-of-the-art multimodality imaging in detecting NO and NOSs, including optical (fluorescence, chemiluminescence, and bioluminescence), electron paramagnetic resonance (EPR), magnetic resonance (MR), and positron emission tomography (PET). With continued effort over the last several years, these noninvasive imaging techniques can now reveal the biodistribution of NO or NOS in living subjects with high fidelity which will greatly facilitate scientists/clinicians in the development of new drugs and/or patient management. Lastly, we will also discuss future directions/applications of NO/NOS imaging. Successful development of novel NO/NOS imaging agents with optimal in vivo stability and desirable pharmacokinetics for clinical translation will enable the maximum benefit in patient management. [Copyright &y& Elsevier]