Molecular SPECT/CT Profiling of Claudin18.2 Expression In Vivo: Implication for Patients with Gastric Cancer.

Zolbetuximab (IMAB362), a monoclonal antibody targeting Claudin18.2 (CLDN 18.2), demonstrates a significant clinical benefit in patients with advanced gastroesophageal cancers. The noninvasive assessment of CLDN18.2 expression through molecular imaging offers a potential avenue for expedited monitoring and the stratification of patients into risk groups. This study elucidates that CLDN18.2 is expressed at a noteworthy frequency in primary gastric cancers and their metastases. The iodogen method was employed to label IMAB362 with 123I/131I. The results demonstrated the efficient and reproducible synthesis of 123I-IMAB362, with a specific binding affinity to CLDN18.2. Immuno-single-photon emission computed tomography (SPECT) imaging revealed the rapid accumulation of 123I-IMAB362 in gastric cancer xenografts at 12 h, remaining stable for 3 days in patient-derived tumor xenograft models. Additionally, tracer uptake of 123I-IMAB362 in MKN45 cells surpassed that in MKN28 cells at each time point, with tumor uptake correlating significantly with CLDN18.2 expression levels. Positron emission tomography/computed tomography imaging indicated that tumor uptake of 18F-FDG and the functional/viable tumor volume in the 131I-IMAB362 group were significantly lower than those in the 123I-IMAB362 group on day 7. In conclusion, 123I-IMAB362 immuno-SPECT imaging offers an effective method for direct, noninvasive, and whole-body quantitative assessment of tumor CLDN18.2 expression in vivo. This approach holds promise for accelerating the monitoring and stratification of patients with gastric cancer.

Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 µg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

Biotin-conjugated Ru(II) complexes with AIE characteristics as mitochondria-targeted photosensitizers for enhancing photodynamic therapy by disrupting cellular redox balance.

The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm-2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics.

Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts in a wide variety of tumors enables a highly selective targeting strategy using FAP inhibitors (FAPIs). Quinoline-based FAPIs labeled with radionuclides have been widely developed for tumor-targeted nuclear medicine imaging. However, the short retention time of FAPIs at the tumor site limits their application in radionuclide therapy. In this study, a novel FAPI-04 dimer was synthesized and labeled with radionuclides to prolong the retention time in tumors for imaging and therapy. To prepare the FAPI-04 dimer complex, DOTA-Suc-Lys-(FAPI-04)2, we used Fmoc-Lys(Boc)-OH as the linker to conjugate two FAPI-04 structures by an amide reaction. The resulting product was further modified by DOTA groups to allow for conjugation with radioactive metals. Both [68Ga]Ga-(FAPI-04)2 and [177Lu]Lu-(FAPI-04)2 showed a radiochemical purity of >99% and remained stable in vitro. In vivo, micro-PET images of SKOV3, A431, and H1299 xenografts revealed that the tumor uptake of [68Ga]Ga-(FAPI-04)2 was about twice that of [68Ga]Ga-FAPI-04 and that the accumulation of [68Ga]Ga-(FAPI-04)2 at the tumor site did not significantly decrease even 3h after injection. The tumor-abdomen ratio of [68Ga]Ga-(FAPI-04)2 images was significantly higher than that of [18F]F-FDG images. For radionuclide therapy, [177Lu]Lu-(FAPI-04)2 effectively retarded tumor growth and displayed good tolerance. In conclusion, the DOTA-Suc-Lys-(FAPI-04)2 design enhanced its uptake in FAP-expressing tumors, improved its retention time at the tumor site, and produced high-contrast imaging in xenografts after radionuclide labeling. Furthermore, it showed a noticeable antitumor effect. DOTA-Suc-Lys-(FAPI-04)2 provides a new approach for applying FAPI derivatives in tumor theranostics.

In vitro and in vivo antitumor activity of novel half-sandwich ruthenium complexes containing quinoline derivative ligands.

A series of half-sandwich ruthenium complexes containing quinoline derivative ligands was synthesized, which had excellent antitumor toxicity toward a variety of cell lines and could localize lysosomes. The damage of lysosomes promotes the release of cathepsin B and initiates downstream apoptotic cascade signals. The increase in reactive oxygen species (ROS) caused by the decrease in mitochondrial membrane potential (ΔΨm) synergistically amplified the damage degree of lysosomes. In addition, the complex could inhibit cell transfer and clone formation. In vivo results showed that the complex had excellent biological effects in tested mouse samples as the body weight of mice did not change much during the treatment, and the mean tumor volume was significantly lower than the control group.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.

Deep learning based on 68Ga-PSMA-11 PET/CT for predicting pathological upgrading in patients with prostate cancer.

Objectives: To explore the feasibility and importance of deep learning (DL) based on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT in predicting pathological upgrading from biopsy to radical prostatectomy (RP) in patients with prostate cancer (PCa). Methods: In this retrospective study, all patients underwent 68Ga-PSMA-11 PET/CT, transrectal ultrasound (TRUS)-guided systematic biopsy, and RP for PCa sequentially between January 2017 and December 2022. Two DL models (three-dimensional [3D] ResNet-18 and 3D DenseNet-121) based on 68Ga-PSMA-11 PET and support vector machine (SVM) models integrating clinical data with DL signature were constructed. The model performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: Of 109 patients, 87 (44 upgrading, 43 non-upgrading) were included in the training set and 22 (11 upgrading, 11 non-upgrading) in the test set. The combined SVM model, incorporating clinical features and signature of 3D ResNet-18 model, demonstrated satisfactory prediction in the test set with an AUC value of 0.628 (95% confidence interval [CI]: 0.365, 0.891) and accuracy of 0.727 (95% CI: 0.498, 0.893). Conclusion: A DL method based on 68Ga-PSMA-11 PET may have a role in predicting pathological upgrading from biopsy to RP in patients with PCa.

Detection of Bone Metastases by 68Ga-DOTA-SSAs and 18F-FDG PET/CT: A Two-Center Head-to-Head Study of Gastroenteropancreatic Neuroendocrine Neoplasms.

Purpose: This study aimed to assess the efficacy of dual-tracer [68Ga-DOTA-somatostatin receptor analogs (SSAs) and 18F-fluorodeoxyglucose (FDG)] positron emission tomography/computed tomography (PET/CT) imaging for detecting bone metastases (BMs) in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods: We retrospectively enrolled 74 GEP-NEN patients with BMs from two centers, who underwent dual-tracer PET/CT from January 2014 to March 2021. We compared and analyzed effectiveness of the dual PET/CT imaging techniques on the BMs, based on 18F-FDG and 68Ga-DOTA-SSAs. Specifically, we analyzed the imaging results using χ 2 tests for classification variables, paired-sample tests for number of BMs, Wilcoxon's signed rank test for number of lesions, and the Kruskal-Wallis test for standard uptake value (SUV) ratio comparison. The correlation of dual-tracer SUVmax with Ki-67 index was analyzed by Spearman's correlation coefficient. Results: The detection efficiencies of dual-tracer PET/CT imaging in patients with different pathologies showed discordant for detecting liver metastases and BMs in group neuroendocrine tumor (NET) G3, 68Ga-DOTA-SSAs was better at detecting BMs for NET G3 (P=0.049 for SUVT/B and P=0.026 for the number of metastatic lesions). In addition, statistical significance was found among osteogenesis group, osteolysis group, and the no-change group (for bone SUVT/B value detected by 18F-FDG and Ki-67 index, osteogenesis group < osteolysis group; for bone SUVT/B detected by 68Ga-DOTA-SSAs, osteogenesis group > the no-change group). What is more, liver and bone SUVmax and Ki-67 index were positively correlated in 18F-FDG imaging (P < 0.001 for liver; P=0.002 for bone), and negatively correlated in 68Ga-DOTA-SSAs imaging (P < 0.001 for liver; P=0.039 for bone). Conclusions: 68Ga-DOTA-SSAs was superior to 18F-FDG for detecting BMs in NET G1/G2 (well and moderately differentiated NETs), as well as in NET G3 (poorly differentiated NETs). Relatively good differentiation was observed in the osteogenesis group. In addition, dual-tracer PET/CT imaging results were observably correlated with tumor differentiation.

Novel Glutathione Activated Smart Probe for Photoacoustic Imaging, Photothermal Therapy, and Safe Postsurgery Treatment.

Preventing tumor recurrence is the most important target for cancer treatment. However, the current effective and advanced technology relies on the use of near-infrared region (NIR), and the equipment of NIR-I and NIR-II fluorescence imaging technique-based fluorescent-guided surgery is expensive and complicated to operate. Here, we report a safe and effective strategy of an organic-inorganic hybrid gold nanoparticle-based novel smart probe (Au@PDA-ss-PEGm NPs) which is appropriate for photoacoustic imaging (PAI) and plasmonic photothermal therapy (PPTT) of tumors in vivo. After intravenous injection, the probe would be transported to the tumor to penetrate the cellular membrane. Then the disulfide bond on the probe surface would be broken with the help of a high concentration of glutathione in the tumor cell. The remaining Au@PDA NPs would aggregate to form plasmonic nanoclusters and exhibit a notable plasmon coupling enhanced photothermal (PCEPT) effect. Besides, the results further proved its good biosafety and pharmacokinetic characteristics in vivo and, more important, a short time exposure under 808 nm laser after surgical removal of the tumor, which would be effective to prevent tumor recurrence and bring dawn to the high-efficiency treatment of tumors.

Treatment of patients with cancer using PD­1/PD­L1 antibodies: Adverse effects and management strategies (Review).

In 2020, there were an estimated 19.3 million new cancer cases and close to 10 million cancer deaths worldwide. Cancer remains one of the leading causes of death. In recent years, with the continuous improvement of our understanding of tumor immunotherapy, immunotherapeutics, such as immune checkpoint inhibitors, have gradually become a hot spot for tumor treatment. Amongst these, programmed cell death protein 1/programmed cell death protein ligand 1 (PD­1/PD­L1) related inhibitors, such as nivolumab and pembrolizumab, atezolizumab, avelumab and durvalumab have been shown to exhibit a high level of efficacy in several types of tumors. It has been confirmed that these inhibitors play an important role in the anti­tumor process, significantly improving the survival rate of patients and delaying the progress of the underlying cancer. However, its method of therapeutic interference and potential for damaging the immune system has caused concern regarding its suitability. As these adverse effects are caused by an immune response to endogenous tissues, they are designated as immune­related adverse events (irAEs). In this review, the typical irAEs reported in recent years and the management strategies adopted are highlighted, to serve as a reference in assessing the clinical response to these adverse reactions.

177Lu-PSMA-I&T Radioligand Therapy for Treating Metastatic Castration-Resistant Prostate Cancer: A Single-Centre Study in East Asians.

Purpose: There is increasing evidence for convincing efficacy and safety of 177Lu-labled prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) for metastatic castration-resistant prostate cancer (mCRPC). However, data are not available regarding the feasibility of 177Lu-labled PSMA-targeted RLT in East Asians. The present study summarized the first experience with 177Lu-PSMA-I&T therapy for mCRPC in China. Methods: Forty consecutive patients with mCRPC were enrolled from December 2019 to September 2021. Eligible patients received 177Lu-PSMA-I&T RLT at intervals of 8-12 weeks. Toxicity was assessed based on standardized physicians' reports and the Common Toxicity Criteria for Adverse Events criteria. Response to PRLT was evaluated according to the changes of prostate specific antigen (PSA) response and imaging response. Quality of life (QOL), Karnofsky performance status (KPS) and pain (visual analogue scale, VAS) were also evaluated. The impacts of baseline parameters on the therapeutic effects were explored by univariate and multivariate logistic regression analyses. Results: All patients underwent a total of 86 cycles of 177Lu-PSMA-I&T (range: 1-5 cycles) with dosages of 3.70-14.43GBq per cycle, with a median of 8 months followed up. Six patients (15%) developed mild reversible xerostomia during follow-up, and 28 patients (70%) experienced grade 1-4 bone marrow dysfunction. Changes in PSA were assessed after therapy, accompanied by the partial response (PR) in 25 patients (62.5%), the stable disease (SD) in 5 patients (12.5%), and the progressive disease (PD) in 10 patients (25%), respectively. QOL, KPS (%) and VAS scores were improved significantly due to treatment (P<0.05). Overweight and elevated AST, ALP, and LDH were associated with poor outcomes. Conclusions: 177Lu-PSMA-I&T achieves the favourable response and well tolerance in mCRPC, which associates with not only PSA decline but also with tumor remission including lymphadenopathy and bone metastasis. We also find that patients with overweight and high AST, ALP, and LDH should be cautious to undergo the PRLT. Large-cohort studies are warranted to confirm the initial findings and elucidate the survival benefit of the treatment.

68Ga-DOTA-NT-20.3 Neurotensin Receptor 1 PET Imaging as a Surrogate for Neuroendocrine Differentiation of Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-negative neuroendocrine prostate cancer (PCa) is a subtype of PCa likely to be lethal, with limited clinical diagnostic and therapeutic options. High expression of neurotensin receptor subtype 1 (NTR1) is associated with neuroendocrine differentiation of PCa, which makes NTR1 a potential target for neuroendocrine PCa. In this study, the NTR1-targeted tracer 68Ga-DOTA-NT-20.3 was synthesized, and its affinity to androgen-dependent (LNCap) and androgen-independent (PC3) xenografts was determined. Methods: 68Ga-DOTA-NT-20.3 was labeled using an automated synthesizer module, and its stability, labeling yield, and radiochemical purity were analyzed by radio-high-performance liquid chromatography. Receptor binding affinity was evaluated in NTR1-positive PC3 cells by a competitive binding assay. The biodistribution of 68Ga-DOTA-NT-20.3 in vivo was evaluated in PC3 and LNCap xenografts by small-animal PET imaging. NTR1 expression was identified by immunohistochemistry and immunofluorescence evaluation. Results: 68Ga-DOTA-NT-20.3 was synthesized successfully, with a yield of 88.07% ± 1.26%, radiochemical purity of at least 99%, and favorable stability. The NTR1 affinity (half-maximal inhibitory concentration) for 68Ga-DOTA-NT-20.3 was 7.59 ± 0.41 nM. Small-animal PET/CT of PC3 xenograft animals showed high-contrast images with intense tumor uptake, which revealed specific NTR1 expression. The tumors showed significant radioactivity (4.95 ± 0.67 percentage injected dose per gram of tissue [%ID/g]) at 1 h, which fell to 1.95 ± 0.17 %ID/g (P < 0.01, t = 8.72) after specific blockage by neurotensin. LNCap xenografts had no significant accumulation (0.81 ± 0.06 %ID/g) of 68Ga-DOTA-NT-20.3 at 1 h. In contrast, 68Ga-PSMA-11 was concentrated mainly in LNCap xenografts (8.60 ± 2.11 %ID/g), with no significant uptake in PC3 tumors (0.53 ± 0.05 %ID/g), consistent with the in vitro immunohistochemistry findings. Biodistribution evaluation showed rapid clearance from the blood and main organs (brain, heart, lung, liver, muscle, and bone), with significantly high tumor-to-liver (4.41 ± 0.73) and tumor-to-muscle (12.34 ± 1.32) ratios at 60 min after injection. Conclusion: 68Ga-DOTA-NT-20.3 can be efficiently prepared with a high yield and high radiochemical purity. Its favorable biodistribution and prominent NTR1 affinity make 68Ga-DOTA-NT-20.3 a potential radiopharmaceutical for the detection of PSMA-negative PCa and identification of neuroendocrine differentiation.

Smart 131 I-Labeled Self-Illuminating Photosensitizers for Deep Tumor Therapy.

Stimulating photosensitizers (PS) by Cerenkov radiation (CR) can overcome the light penetration limitation in traditional photodynamic therapy. However, separate injection of radiopharmaceuticals and PS cannot guarantee their efficient interaction in tumor areas, while co-delivery of radionuclides and PS face the problem of nonnegligible phototoxicity in normal tissues. Here, we describe a 131 I-labeled smart photosensitizer, composed of pyropheophorbide-a (photosensitizer), a diisopropylamino group (pH-sensitive group), an 131 I-labeled tyrosine group (CR donor), and polyethylene glycol, which can self-assemble into nanoparticles (131 I-sPS NPs). The 131 I-sPS NPs showed low phototoxicity in normal tissues due to aggregation-caused quenching effect, but could self-produce reactive oxygen species in tumor sites upon disassembly. Upon intravenous injection, 131 I-sPS NPs showed great tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice and orthotopic VX2 liver tumor bearing rabbits. We believed 131 I-sPS NPs could expand the application of CR and provide an effective strategy for deep tumor theranostics.

[99mTc]Tc-Galacto-RGD2 integrin αvß3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [99mTc]Tc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αvß3 expression, and neovascularization in lung cancer subtypes was also addressed. METHODS: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [99mTc]Tc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [99mTc]Tc-Galacto-RGD2 was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αvß3, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours. RESULTS: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [99mTc]Tc-Galacto-RGD2 SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αvß3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvß3 expression. Integrin αvß3 expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αvß3 expression. CONCLUSIONS: [99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.

Cetuximab functionalization strategy for combining active targeting and antimigration capacities of a hybrid composite nanoplatform applied to deliver 5-fluorouracil: toward colorectal cancer treatment.

Antibody-functionalized targeted nanocarriers to deliver chemotherapeutics have been widely explored. However, it remains highly desirable to understand and apply the antitumor potential of antibodies integrated in hybrid composite nanoplatforms. Herein, mesoporous silica nanoparticles, a supported lipid bilayer and cetuximab were integrated to fabricate a hybrid nanoplatform for effectively encapsulating and selectively delivering 5-fluorouracil (5-FU) against colorectal cancer (CRC) cells. The specially designed nanoplatform exhibited superior properties, such as satisfying size distribution, dispersity and stability, drug encapsulation, controlled release, and cellular uptake. Interestingly, the modification of cetuximab onto nanoplatforms without drug loading can significantly inhibit the migration and invasion of CRC cells through suppressing the epidermal growth factor receptor (EGFR)-associated signaling pathway. Furthermore, delivery of 5-FU by using this nanoplatform can remarkably induce cytotoxicity, cell cycle arrest, and cell apoptosis for CRC cells with high EGFR expression. Overall, this nanostructured platform can dramatically improve the tumor killing effects of encapsulated chemotherapeutics and present antimigration effects derived from the antibody modified on it. Moreover, in vivo biodistribution experiments demonstrated the superior tumor targeting ability of the targeted nanoparticles. Thus, this targeted nanoplatform has substantial potential in combinational therapy of antibodies and chemotherapy agents against colorectal cancer.

Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

DNA origami: an outstanding platform for functions in nanophotonics and cancer therapy.

Due to the proposal and evolution of the DNA origami technique over the past decade, DNA molecules have been utilized as building blocks for the precise construction of nanoscale architectures. Benefiting from the superior programmability of DNA molecules, the sequence-dependent recognition mechanism and robust complementation among DNA strands make it possible to customize almost arbitrary structures. Such an assembly strategy bypasses some of the limits of conventional fabrication methods; the fabrication accuracy and complexity of the target product are unprecedentedly promoted as well. Furthermore, due to the spatial addressability of the final products, nanostructures assembled through the DNA origami technique can also serve as a versatile platform for the spatial positioning of functional elements, represented by colloidal nanoparticles (NPs). The subsequent fabrication of heterogeneous functional nanoarchitectures is realized via modifying colloidal NPs with DNA strands and manipulating them to anchor into DNA origami templates. This has given rise to investigations of their novel properties in nanophotonics and therapeutic effects towards some diseases. In this review, we survey the crucial progress in the development of DNA origami design, assembly and structural analysis and summarize available applications in nanophotonics and cancer therapy based on the object-dressed DNA origami complex. Moreover, we elucidate the development of this field and discuss the potential directions of this kind of application-oriented nanomanufacturing.

[Positive rate and accuracy of ultrasound-guided fine-needle aspiration cytology for detecting suspected thyroid carcinoma nodules of different sizes].

OBJECTIVE: To analyze the accuracy and positive rate of ultrasound-guided fine-needle aspiration (US-FNA) cytology for detecting suspected thyroid cancer nodules of different sizes. METHODS: A total of 591 patients with 594 suspected malignant thyroid nodules received examinations with US-FNA cytology. Based on their size, the nodules were divided into group I (4-5 mm), group II (6-10 mm), group III (>10 mm). With the results of pathology as the standard, we analyzed the results of US-FNA cytology for detecting thyroid carcinoma in terms of its accuracy, indeterminate rate, positive predictive value and negative predictive value for nodules of different sizes. RESULTS: The positive rates in group I, group II and group III were 39.2% (40/102), 48.2% (172/357) and 65.2% (88/135), respectively, similar between groups I and II (P=0.107) and differed significantly between groups I and III (P=0.000) and between groups II and III (P=0.001). The accuracy, indeterminate rate, positive predictive value and negative predictive value in the 3 groups were 95.5% (21/22), 97.1% (100/103), and 94.4% (51/54); 2.9% (3/102), 2.8% (10/357), and 1.5% (2/135); 100%, 100%, and 98%; 66.7%, 57.1%, and 33.3%, respectively, showing no significant differences among the 3 groups. CONCLUSIONS: The size of the thyroid nodules can affect the positive rate but does not have significant effects on the accuracy, indeterminate rate, positive predictive value or negative predictive value of US-FNA cytology.

Contribution of soybean polysaccharides in digestion of oil-in-water emulsion-based delivery system in an in vitro gastric environment.

This study aims to evaluate the effects of soy soluble polysaccharide and soy hull polysaccharide on stability and characteristics of emulsions stabilised by soy protein isolate in an in vitro gastric environment. Zeta potential and particle size were used to investigate the changes of physico-chemical and stability in the three emulsions during in vitro gastric digestion, following the order: soy protein isolate-stability emulsion < soy protein isolate-soy soluble polysaccharide -stability emulsion < soy protein isolate-soy hull polysaccharide-stability emulsion, confirming that coalescence in the soy protein isolate-stability emulsion occurred during in vitro gastric digestion. Optical microscopy and stability measurement (backscattering) also validate that addition of polysaccharide (soy soluble polysaccharide and soy hull polysaccharide) can reduce the effect of simulated gastric fluid (i.e., pH, ionic strength and pepsin) on emulsion stability, especially, soy protein isolate-soy hull polysaccharide-stability emulsion, compared with soy protein isolate-stability emulsion. This suggests that the flocculation behaviours of these emulsions in the stomach lead to a difference in the quantity of oil and the size and structure of the oil droplets, which play a significant role in emulsion digestion in the gastrointestinal tract. This work may indicate a potential application of soy hull polysaccharide for the construction of emulsion food delivery systems.