SUV max as Predictor of Metastatic Disease on 18 F-FDG PET-CT in Hepatocellular Carcinoma.

OBJECTIVE: To ascertain the utility of maximum standardised uptake value (SUVmax) in 18F-FDG PET-CT in predicting metastatic disease burden in hepatocellular carcinoma (HCC) patients. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Nuclear Medicine and PET-CT Imaging, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan, from April to October 2022. METHODOLOGY: 18F-FDG PET-CT data of 87 patients were analysed prospectively. Patients were considered regardless of resection status. The SUVmax measurements were performed, and their association with metastases was determined. Molecular docking studies were conducted to determine a mechanism behind the higher SUVmax at the metastatic sites. RESULTS: A higher number of patients (49) was found to have metastasis (1 to 5 in numbers) and demonstrated higher SUVmax, especially in cases of pre-surgery and post-transplant state. A positive correlation existed between SUVmax of pre-surgery (r = 0.419, p = 0.001) and post-transplant patients (r = 0.779, p = 0.001). Molecular docking studies revealed a strong binding affinity (-5.18± 0.25 kcal/mol) between the hexokinase (HK-II) and 18F-FDG. CONCLUSION: SUVmax positively correlated with metastatic tumour burden. The strong binding affinity between the HK-II and 18F-FDG may be the reason. 18F-FDG PET-CT appeared beneficial in providing prognostic information for HCC in a selected group. KEY WORDS: Hepatocellular carcinoma, 18F-FDG, Positron emission tomography, Maximum standardised uptake value, SUVmax, HK-II binding, PET-CT, Metastases.

Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma.

Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches exhibit promise in GBM treatment; however, the successful translation of these strategies from preclinical models to clinical settings is hindered by inefficient nanoparticle clearance from vital organs. Addressing this concern, we investigated the therapeutic potential of amrubicin (AMR) encapsulated within poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) in combating temozolomide (TMZ) resistant GBM. The study demonstrated that AMR-PLGA-NPs exerted a pronounced inhibitory effect on the cellular viability and migratory capacity of TMZ-resistant GBM cells. Furthermore, these nanoparticles exhibited considerable efficacy in downregulating the PI3K/AKT signaling pathway, thereby inducing apoptosis specifically in TMZ-resistant glioma cells and glioma stem-like cells through the activation of PTEN. Notably,in vivoexperimentation revealed the ability of AMR-PLGA-NPs to traverse biological barriers within murine models. Collectively, these findings underscore the potential therapeutic utility of AMR-PLGA-NPs as a versatile nanoplatform for addressing the formidable challenges posed by GBM, particularly in mitigating drug resistance mechanisms. The study substantiates the stability and safety profile of AMR-PLGA-NPs, positioning them as a promising avenue for combating drug resistance in GBM therapeutics.

Synthesis, biological and molecular docking studies of pyrimidine-derived bioactive Schiff bases.

Pyrimidine which is an important constituent of the genetic material of deoxyribonucleic acid, is identified with a large number of biological activities. Based on this, pyrimidine-derived Schiff bases (1-6) of hydroxy-1-naphthaldehyde were synthesized by using the condensation method. In addition, the molecular docking studies against topoisomerase II DNA gyrase, human hematopoietic cell kinase, urate oxidase from Aspergillus flavus, and cyclin-dependent kinase 8 to explore the antibacterial, antioxidant, antifungal, and anticancer properties respectively and binding affinities through bioinformatics approaches to determine the interaction among active molecules with the receptor. Hence, the computational docking analyses identified that all synthesized pyrimidine Schiff bases (1-6) are active and exhibited better binding affinities as compared to the standard drugs. Furthermore, all the prepared materials were characterized by using nuclear magnetic resonance, infrared, and elemental analysis. Additionally, the phase-transition and thermal decomposition temperatures were determined by differential scanning calorimetry and thermo-gravimetric analysis measurements. Moreover, the structures of pyrimidine-derived Schiff bases 1, 2, 3, 4, and 5 were also confirmed by the X-ray single-crystal diffraction technique. The pyrimidine-derived Schiff bases 5 possess significant antibacterial, antioxidant, antifungal, and anticancer agent properties which confirms its promising biological activities over standard drugs.

Gallbladder Emulating Hepatic Haemangioma On Gastrointestinal Bleed Scan.

Tc-99m labelled erythrocyte scan is a sensitive method for detection of gastrointestinal (GI) bleed and liver haemangioma but false positive results can occur, as in this case gallbladder is visualized which is not a common finding. Single­photon emission computed tomography/computed tomography (SPECT-CT) is helpful to avoid such false­positive results.

68Ga-PSMA PET-CT and PSMA score affecting therapeutic decision-making in high-risk prostatic carcinoma.

Purpose: This research study was conducted to evaluate the impact of (68Ga)-tagged prostatic-specific membrane antigen (68Ga-PSMA) positron emission tomography and computed tomography (PET-CT), compare its role with conventional radiology in early staging of high-risk prostate cancer, and calculate the PSMA score evaluating its usefulness in 68Ga-PSMA PET-CT reporting in our patient population. Material and methods: 68Ga-PSMA PET-CT of 65 high-risk cases of prostate cancer was performed for staging purpo-ses. Any change in disease stage was noted after 68Ga-PSMA PET-CT findings and PSMA score leading to a change in the management plan. Results: Change in disease stage post-PSMA imaging was seen in 39% cases, high PSMA score (03) was noted in > 80% of upstaged cases, while low score (0) and (1) was seen in 65% and 35% down-staged individuals, respectively. Change in therapeutic decision-making was observed in 32% (21) of patients. Conclusions: 68Ga-PSMA PET-CT scans have a significant influence on the planned clinical management of high-risk prostate cancer patients; hence, they can be utilized as a replacement for radiological imaging tools, particularly in the detection of pelvic nodal and distant metastatic disease. PSMA score can be considered as an effective tool in standardized reporting of 68Ga-PSMA imaging.

Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.

BACKGROUND: Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer. METHODS: Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM. RESULTS: Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity. CONCLUSION: This study provides an avenue for specific BLM therapeutics with minimal side effects.

Synergistic therapeutic antitumor effect of PD-1 blockade cellular vesicles in combination with Iguratimod and Rhodium nanoparticles.

Immune checkpoint blockade has emerged as a significant therapeutic development in immunotherapy during the past decade. However, only a small percentage of cancer patients respond to checkpoint blockade, suggesting that a fundamental knowledge of the underlying processes of immune checkpoint receptor signaling remains elusive and that novel therapeutic medications are needed. Here, the programmed cell death protein 1(PD-1) expressing nanovesicles were developed to enhance T cell activity. Iguratimod (IGU) and Rhodium (Rh) nanoparticles (NPs) were loaded in PD-1 nanovesicles (NVs) for synergistic therapeutic antitumor effects against lung cancer and metastasis. For the first time, this study revealed that IGU exhibits an antitumor effect by inhibiting the phosphorylation of mammalian target of rapamycin (mTOR) and Rh-NPs provided a photothermal effect by improving reactive oxygen species (ROS)-dependent apoptosis in lung cancer cells. IGU-Rh-PD-1 NVs also reduced the migration ability through the epithelial-mesenchymal transition (EMT) pathway. Furthermore, IGU-Rh-PD-1 NVs reached the targeted site and inhibited tumor growth in vivo. This strategy could boost T cell performance and simultaneously possess chemotherapeutic and photothermal therapy to serve as a new combination therapy for lung cancer and potentially other aggressive cancer.

Nanosheet arrays of iron oxide for enhanced ammonia synthesis via electrochemical nitrogen reduction for prospective algal membrane bioreactors.

The earth's nitrogen cycle relies on the effective conversion of nitrogen (N2) to ammonia (NH3). As a result, the research and development of catalysts that are earth-abundant, inexpensive, and highly efficient but do not need precious metals is of the utmost significance. In this investigation, we present a controlled synthesis technique to the fabrication of an iron oxide (Fe2O3) nanosheet array by annealing at temperatures ranging from 350 to 550 °C. This array will be used for the electrochemical reduction of atmospheric N2 to NH3 in electrolytes. The Fe2O3 nanosheet array that was produced as a result displays outstanding electrochemical performance as well as remarkable stability. When compared to a hydrogen electrode working under normal temperature and pressure conditions, the Fe2O3 nanosheet array produces an impressive NH3 production rate of 18.04 g per hour per mg of catalytically active material in 0.1 M KOH electrolyte, exhibiting an enhanced Faradaic efficiency (FE) of 13.5% at -0.35 V. This is accomplished by exhibiting an enhanced Faradaic efficiency (FE) of 0.1 M KOH electrolyte. The results of experiments and electrochemical studies reveal that the existence of cation defects in the Fe2O3 nanosheets plays an essential part in the enhancement of the electrocatalytic activity that takes place during nitrogen reduction reactions (NRR). This study not only contributes to the expanding family of transition-metal-based catalysts with increased electrocatalytic activity for NRR, but it also represents a substantial breakthrough in the design of catalysts that are based on transition metals, so it's a win-win. In addition, the use of Fe2O3 nanosheets as electrocatalysts has a lot of potential in algal membrane bioreactors because it makes nitrogen fixation easier, it encourages algae growth, and it makes nitrogen cycling more resource-efficient.

Lutetium-177 Prostate Specific Membrane Antigen Therapy in a Patient With Double Malignancy and Single Functioning Kidney: A Case Report.

Lutetium-177 labeled with 617 types of Prostate Specific Membrane Antigen (177Lu PSMA-617) Radio-ligand Therapy (RLT) is an emerging modality of choice for the treatment of metastatic castration-resistant prostate carcinoma (mCRPC). After it is administered intravenously, it is excreted primarily through the kidneys. Physiological excretion and concomitant expression of PSMA receptors on renal tissues are associated with potential renal toxicity, a matter of concern while treating patients with multiple doses of RLT. There are published articles that have demonstrated the safe use of 177Lu PSMA-617 in patients with bilateral fair-functioning kidneys; however, only a single study has been published that has evaluated its safety in patients with solitary-functioning kidneys. The uniqueness of this case report lies in the fact that we have documented the renal safety profile of 177Lu PSMA-617 therapy after multiple doses in a patient who presented with double malignancy (metastatic castration-resistant prostate carcinoma and left renal cell carcinoma) and had a single-functioning right kidney.

Renal tumoural calcinosis: Extensive and multifocal form.

Renal tumoural calcinosis is rare, but the incidence is rising with increasing life expectancy due to dialysis. Whole body skeletal scintigraphy with 99mTc- MDP is a sensitive method to detect sites of osseous involvement. We share an interesting image of the bone scan, in a patient with extensive renal tumoural calcinosis.

Reversing Immune Suppression and Potentiating Photothermal Immunotherapy via Bispecific Immune Checkpoint Inhibitor Loaded Hollow Polydopamine Nanospheres.

Despite the great achievements of immune checkpoint blockade (ICB) therapy on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis, ICB monotherapy still faces obstacles in eradicating solid tumors due to the lack of tumor-associated antigens or tumor-specific cytotoxicity. Photothermal therapy (PTT) is a potential therapeutic modality because it can noninvasively kill tumor cells by thermal ablation and generate both tumor-specific cytotoxicity and immunogenicity, which holds great feasibility to improve the efficiency of ICB by providing complementary immunomodulation. Except for the PD-1/PD-L1 axis, the cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRPα) pathway has been considered as a novel strategy of tumor cells to evade the surveillance of macrophages and inactivate the immune response of PD-L1 blockade therapy. Therefore, it is necessary to synergize the antitumor effect of dual-targeting PD-L1 and CD47. Although promising, the application of PD-L1/CD47 bispecific antibodies, especially in combination with PTT, remains a formidable problem, due to the low objective response, activity loss at relatively high temperature, or nonvisualization. Herein, instead of using antibodies, we use MK-8628 (MK) to down-regulate both PD-L1 and CD47 simultaneously through halting the active transcription of oncogene c-MYC, leading to elicitation of the immune response. The hollow polydopamine (HPDA) nanospheres are introduced as a biocompatible nanoplatform with high loading capacity and magnetic resonance imaging (MRI) ability to deliver MK and induce PTT (HPDA@MK). Compared to preinjection, HPDA@MK exhibits the strongest MRI signal at 6 h postintravenous injection to guide the precise combined treatment time. However, due to the local delivery and controlled release of inhibitors, HPDA@MK down-regulates c-MYC/PD-L1/CD47, promotes the activation and recruitment of cytotoxic T cells, regulates the M2 macrophages polarization in tumor sites, and especially boosts the combined therapeutic efficacy. Collectively, our work presents a simple but distinctive approach for c-MYC/PD-L1/CD47-targeted immunotherapy combined with PTT that may provide a desirable and feasible strategy for the treatment of other clinical solid tumors.

Self-Assembled Carrier-Free Nanodrugs for Starvation Therapy-Amplified Photodynamic Therapy of Cancer.

Traditional starvation treatment strategies, which involve glucose oxidase and drug-induced thrombi, often suffer from aggravated tumor hypoxia and have failed to improve antitumor efficacy in combination with oxygen-dependent photodynamic therapy (PDT). Herein, glucose transporter 1 inhibitor genistein (Gen) and photosensitizer chlorin e6 (Ce6) are integrated to construct carrier-free self-assembled nanoparticles defined as GC NPs, for starvation therapy-amplified PDT of tumor. GC NPs with regular morphology and stability are screened out by component adjustment, while the function of each component is preserved. On the one hand, Gen released from GC NPs can cut off tumor glucose uptake by inhibiting the glucose transporter 1 to restrict tumor growth, achieving starvation therapy. On the other hand, they are able to decrease the amount of oxygen consumed by tumor respiration and amplify the therapeutic effect of PDT. In vitro and in vivo experiments verify the excellent synergistic antitumor therapeutic efficacy of GC NPs without any apparent toxicity. Moreover, fluorescence and photoacoustic imaging provide guidance for in vivo PDT, demonstrating the excellent tumor enrichment efficiency of GC NPs. It is believed that this starvation therapy-amplified PDT strategy by carrier-free self-assembled GC NPs holds promising clinical prospects.

Precision Delivery of Dual Immune Inhibitors Loaded Nanomodulator to Reverse Immune Suppression for Combinational Photothermal-Immunotherapy.

Although photothermal therapy (PTT) can noninvasively kill tumor cells and exert synergistic immunological effects, the immune responses are usually harmed due to the lack of cytotoxic T cells (CTLs) pre-infiltration and co-existing of intricate immunosuppressive tumor microenvironment (TME), including the programmed cell death ligand 1 (PD-L1)/cluster of differentiation 47 (CD47)/regulatory T cells (Tregs)/M2-macrophages overexpression. Indoleamine 2, 3-dioxygenase inhibitor (NLG919) or bromodomain extra-terminal inhibitor (OTX015) holds great promise to reprogram suppressive TME through different pathways, but their collaborative application remains a formidable challenge because of the poor water solubility and low tumor targeting. To address this challenge, a desirable nanomodulator based on dual immune inhibitors loaded mesoporous polydopamine nanoparticles is designed. This nanomodulator exhibits excellent biocompatibility and water solubility, PTT, and bimodal magnetic resonance/photoacoustic imaging abilities. Owing to enhanced permeability and retention effect and tumor acidic pH-responsiveness, both inhibitors are precisely delivered and locally released at tumor sites. Such a nanomodulator significantly reverses the immune suppression of PD-L1/CD47/Tregs, promotes the activation of CTLs, regulates M2-macrophages polarization, and further boosts combined therapeutic efficacy, inducing a strong immunological memory. Taken together, the nanomodulator provides a practical approach for combinational photothermal-immunotherapy, which may be further broadened to other "immune cold" tumors.

Peptide functionalized actively targeted MoS2 nanospheres for fluorescence imaging-guided controllable pH-responsive drug delivery and collaborative chemo/photodynamic therapy.

The combination of imaging and different therapeutic strategies into one single nanoplatform often demonstrates improved efficacy over monotherapy in cancer treatments. Herein, a multifunctional nanoplatform (labelled as MPRD) based on molybdenum disulfide quantum dots (MoS2 QDs) is developed to achieve enhanced antitumor efficiency by integrating fluorescence imaging, tumor-targeting and synergistic chemo/photodynamic therapy (PDT) into one system. First, polyethylene glycol (PEG)ylated MoS2 QDs (MP) with desirable stability are synthesized via a hydrothermal process using MoS2 QDs and carboxyamino-terminated oligomeric PEG as raw materials. Then, MP were conjugated with arginine-glycine-aspartic acid (RGD) peptide via amidation to form a novel nanocarrier (MPR), which possesses strong blue fluorescence, good biocompatibility and ανß3 receptor-mediated targeting ability. More importantly, MPR generated reactive oxygen species under 808 nm laser activation to realize targeted antitumor PDT. Further doxorubicin (DOX) was loaded onto MPR, which endows MPRD with localized chemotherapy and pH-responsive drug release. The MPRD exhibits improved chemotherapy performance on HepG2 cells (overexpressing integrin ανß3) owing to enhanced cellular uptake mediated by ανß3 receptor and effective drug release triggered by intracellular pH. Notably, MPRD with efficient tumor targeting ability and high chemo/PDT efficacy under NIR laser irradiation is capable of inhibiting HepG2 tumor cell growth both in vitro and in vivo, which is significantly superior to each individual therapy. These findings demonstrate that MPRD holds great potential in effective cancer therapy.

Dye-cored polylysine dendrimer as luminescent nanoplatform for imaging-guided anticancer drug delivery.

Dendrimers have numerous applications in imaging and drug delivery. Designing a dendrimer diagnostic platform with a well-defined structure and controlled drug delivery is a formidable challenge. Here, we design dendritic polymer-platinum conjugates (G5-PEG-Pt) as pH-responsive nanovesicles for imaging-guided platinum drug delivery. The G5-PEG-Pt have a well-defined structure, intrinsically bright fluorescence, and acid-responsive drug release. The pH-responsive G5-PEG-Pt could rapidly release the platinum drug at acidic pH (5.0) than neutral pH (7.4). The G5-PEG-Pt could enter SKOV-3 human ovarian cancer cells by the endocytosis pathway and exhibited comparative cytotoxicity to free cisplatin. By virtue of the prolonged blood circulation time and the enhanced permeability and retention (EPR) effect, a 4.4-fold higher tumor platinum uptake than that of free cisplatin was achieved, potentially enhancing the therapeutic indexes of the platinum drug. Therefore, these pH-responsive platinum and fluorescent dendrimer conjugates are expected to be potent in vivo cancer optical imaging and therapy platforms.

Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

Acidity/carbon dioxide-sensitive triblock polymer-grafted photoactivated vesicles for programmed release of chemotherapeutic drugs against glioblastoma.

Controllable release of chemotherapeutic drugs in tumor sites remains a big challenge for precision therapy. Herein, we developed acidity/carbon dioxide (H+/CO2)-sensitive poly (ethylene glycol)-b-poly (2-(diisopropylamino) ethyl methacrylate)-b-polystyrene triblock polymer (PEG-b-PDPA-b-PS) grafted photoactivated vesicles for programmed release of chemotherapeutic drugs against glioblastoma. In brief, gold nanoparticles (GNPs) were firstly tethered with the H+/CO2-sensitive PEG-b-PDPA-b-PS polymer. Next, the CO2 precursor (ammonium bicarbonate, NH4HCO3) and doxorubicin (DOX) were loaded during self-assembly process of PEG-b-PDPA-b-PS-tethered GNPs, thus obtaining the multifunctional gold vesicles (denoted as GVND). The programmed multi-stimuli responsive drug release by GVND was undergone in multiple steps as follows: 1) the vesicular architecture of GVND was first swelled in tumor acidic microenvironment, 2) the GVND were partially broken under near-infrared (NIR) laser irradiation, 3) the mild hyperthermia generated by GV triggered the thermal decomposition of encapsulated NH4HCO3, leading to the in situ generation of CO2, 4) the generated CO2 reacted with PDPA of PEG-b-PDPA-b-PS, changing the hydrophilicity and hydrophobicity of GVND, thus vastly breaking its vesicular architecture, finally resulting in a "bomb-like" release of DOX in tumor tissues. Such a multi-stimuli responsive programmed drug delivery and mild hyperthermia under NIR laser activation displayed strong antitumor efficacy and completely eradicated U87MG glioblastoma tumor. This work presented a promising strategy to realize precision drug delivery for chemotherapy against glioblastoma. STATEMENT OF SIGNIFICANCE.

Detection of Primary Hepatocellular Carcinoma on 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography.

Aims and background: Hepatocellular carcinoma (HCC), ranks as the third most prevalent malignancy contributing to cancer-related death on a global scale. Hepatocellular carcinoma is known to be the fifth most frequently diagnosed malignancy of the males while among females, it is ranked as the seventh most common malignancy. The study was conducted to detect the sensitivity of primary HCC using 18F-flourodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan. Materials and methods: This prospective study was conducted to identify the primary HCC in a sample size of 51 patients, in whom FDG PET-CT scan was performed between May 2022 and December 2022. Results: Among the cohort of 51 patients, primary HCC was detected on FDG PET-CT in 43 individuals representing true-positive cases. Conversely, FDG PET-CT was unable to detect HCC in 8 cases, representing false-negative. Out of 51 patients, 74.5% of HCC cases exhibited multifocal pattern. The maximum standardized uptake value (SUV max) of the primary malignant site ranged from 1.9 to 16.1, with a mean of 3.7 ± 2.8. The FDG PET-CT revealed abnormal sites of the uptake outside liver in 23 individuals. The research confirmed the tumor recurrence in four previously treated patients. In the conducted investigation, FDG PET-CT showed 84.3% sensitivity for the diagnosis of HCC. Conclusion: The study demonstrates that FDG PET-CT is a viable option for the detection of HCC. The sensitivity of FDG PET-CT in our population is comparable and in agreement with international data for diagnosis of HCC thereby favoring its reproducibility among geographical and ethnic groups. However, owing to the reduced ability of FDG PET-CT scan to identify well-differentiated/low-grade HCC, the routine use of FDG PET-CT scan may not be considered in cases requiring evaluation of primary disease only. How to cite this article: Arshad K, Hanan SD, Younis MN, et al. Detection of Primary Hepatocellular Carcinoma on 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography. Euroasian J Hepato-Gastroenterol 2023;13(2):66-72.

Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors.

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.

Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy.

5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.