Preparation, Biological Evaluation, and First-in-Human Single-Photon Emission Computed Tomography (SPECT) Study of 99mTc-Labeled Prostate-Specific Membrane Antigen (PSMA)-Targeted Radiotracers Containing Triazole with Reduced Kidneys Accumulation.

Prostate-specific membrane antigen (PSMA), a well-established biological marker for prostate cancer (PCa) imaging and therapy, is overexpressed on the surface of prostate cancer lesions. In this study, a triazole ring was introduced into the linker by click chemistry to generate a HYNIC-derived ligand (T), which exhibited good PSMA affinity (Ki = 2.23 nM). Eight stable 99mTc-labeled complexes, [99mTc]Tc-T-Mn (n = 1-8), with hydrophilic properties were synthesized by incorporating different coligands at high radiochemical yields and purities without purification. The radioligands were concentrated in the kidneys of healthy Kunming male mice and were significantly blocked by the PSMA inhibitor ZJ-43. The uptake of the optimized complex [99mTc]Tc-T-M2 was correlated with PSMA, and it had good PSMA affinity (Kd = 5.42 nM). [99mTc]Tc-T-M2 accumulated on LNCaP (PSMA++) tumors and was significantly blocked by ZJ-43 at 2 h p.i., indicating high PSMA specificity. Relatively suitable kidney uptake was beneficial for reducing kidneys exposure in patients. SPECT/CT imaging of [99mTc]Tc-T-M2 in LNCaP (PSMA++) or 22Rv1 (PSMA+) tumor-bearing mice revealed high tumor uptake, low background uptake (especially low kidney uptake (49.06 ± 9.20 %ID/g) at 2 h p.i.), and obvious inhibition by ZJ-43, whereas PC-3 (PSMA-) tumors were undetectable. A freeze-dried [99mTc]Tc-T-M2 kit was successfully developed (T-M2 kit). Preliminary clinical trials showed that [99mTc]Tc-T-M2 clearly identified small prostate cancer lesions and has potential for clinical application.

A nomogram to predict the risk of venous thromboembolism in patients with colon cancer in China.

OBJECTIVE: To create a nomogram for predicting the likelihood of venous thromboembolism (VTE) in colon cancer patients from China. METHODS: The data of colon cancer patients from Chongqing University Cancer Hospital between 2019 and 2022 were analyzed. Patients were divided into training set and internal validation set by random split-sample method in a split ratio of 7:3. The univariable and multivariable logistic analysis gradually identified the independent risk factors for VTE. A nomogram was created using all the variables that had a significance level of p < 0.05 in the multivariable logistic analysis and those with clinical significance. Calibration curves and clinical decision curve analysis (DCA) were used to assess model's fitting performance and clinical value. Harrell's C-index (concordance statistic) and the area under the receiver operating characteristic curves (AUC) were used to evaluate the predictive effectiveness of models. RESULTS: A total of 1996 patients were ultimately included. There were 1398 patients in the training set and 598 patients in the internal validation set. The nomogram included age, chemotherapy, targeted therapy, hypertension, activated partial thromboplastin time, prothrombin time, platelet, absolute lymphocyte count, and D-dimer. The C-index of nomogram and Khorana score were 0.754 (95% CI 0.711-0.798), 0.520 (95% CI 0.477-0.563) in the training cohort and 0.713 (95% CI 0.643-0.784), 0.542 (95% CI 0.473-0.612) in the internal validation cohort. CONCLUSIONS: We have established and validated a nomogram to predict the VTE risk of colon cancer patients in China, which encompasses a diverse age range, a significant population size, and various clinical factors. It facilitates the identification of high-risk groups and may enable the implementation of targeted preventive measures.

68Ga-FAPI-04 PET/CT Imaging of Mesenteric Aggressive Fibromatosis.

ABSTRACT: Aggressive fibromatosis is a relatively rare disease. We describe 68Ga-FAPI-04 PET/CT findings in a case of histologically proved mesenteric aggressive fibromatosis. 68Ga-FAPI-04 PET/CT revealed a mass in the mesentery with increased FAPI activity. This case indicates that FAPI PET may be useful for evaluation of aggressive fibromatosis.

68 Ga-DOTATATE and 68 Ga-FAPI Imaging in Neuroendocrine Neoplasms of Different Grades.

ABSTRACT: We report findings from 68 Ga-DOTATATE and 68 Ga-FAPI PET/CT in a 43-year-old woman with neuroendocrine neoplasms. DOTATATE and FAPI uptake differed in different lesions. These results suggest a potential value for dual-tracer imaging in the evaluation of neuroendocrine neoplasms that have different grades.

Solitary Pulmonary Perivascular Epithelial Cell Tumor Mimicking Pulmonary Metastasis on 68 Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor.

ABSTRACT: We report the findings of 68 Ga-DOTATATE PET/CT in a 56-year-old woman with solitary pulmonary perivascular epithelioid cell tumor. 68 Ga-DOTATATE PET/CT showed a lesion with intense uptake in the region of pancreatic head and a solitary nodule with moderate uptake in the left lung. Pancreatic neuroendocrine tumor with pulmonary metastasis was considered. The postoperative pathological results showed a benign perivascular epithelioid cell tumor of the lung. This case emphasizes the need to increase awareness of benign perivascular epithelioid cell tumors in the differential diagnosis of solitary pulmonary nodule with moderate DOTATATE activity.

Elevated 68 Ga-FAPI Activity in Leiomyosarcoma.

ABSTRACT: Leiomyosarcoma is an aggressive subtype of soft tissue sarcoma with frequent metastatic relapse after curative surgery. Herein, we report the 68 Ga-FAPI PET/CT findings in a 45-year-old woman with leiomyosarcoma. 68 Ga-FAPI-04 PET/CT detected increased FAPI uptake in abdominal leiomyosarcoma and liver metastases. The positive findings of 68 Ga-FAPI in this case highlighted that 68 Ga-FAPI may have potential value in the evaluation of leiomyosarcoma.

Chlorogenic Acid Inhibits Proliferation, Migration and Invasion of Pancreatic Cancer Cells via AKT/GSK-3ß/ß-catenin Signaling Pathway.

BACKGROUND: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated. OBJECTIVE: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells. METHODS: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3ß/ß-catenin signaling pathway was detected by Western Blot. RESULTS: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3ß(Ser9), ß-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells. CONCLUSION: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3ß/ß-catenin signaling pathway.

18 F-FDG PET/CT Findings of Ovarian Myxoid Chondrosarcoma.

ABSTRACT: Ovarian myxoid chondrosarcoma is a rare and aggressive tumor. We present 18 F-FDG PET/CT findings of ovarian myxoid chondrosarcoma. The images not only demonstrated a pelvic mass with increased FDG uptake, but also a mass with increased FDG uptake in the right lower abdominal wall. Ovarian malignancy with abdominal wall metastases was suspected. An extraskeletal myxoid chondrosarcoma was diagnosed histopathologically after the mass excision.

The characteristics and comparison between young and old patients with spontaneous isolated celiac artery dissection: Analysis based on 60 reports.

BACKGROUND AND AIMS: Though increasing studies reported the management of spontaneous isolated celiac artery dissection (ICAD), the characteristics and etiology of ICAD in different age-stage patients have not been well-studied. Our study was designed to describe and further to compare the clinical features of spontaneous ICAD between young and old patients. METHODS: We searched PubMed, Embase, and Web of Science up to March 1, 2023 for spontaneous ICAD case reports. Two reviewers screened the titles and abstracts of searched records for qualified reports according to the including and excluding criteria and extracted the data independently. Statistical analysis was performed using SPSS software (version 19.0; IBM Corp, Armonk, NY) and Stata 12.0 (Stata Corp., College Station, TX). Descriptive results were presented as the mean ±â€…standard deviation or percent. The comparison results between young and old patients were displayed as risk ratio (RR) or standardized mean difference (SMD) with its 95% confidence intervals (CI). RESULTS: We totally identified 60 reports in the present analysis. The mean age of patients was 52.4 years, with the majority of patients being male (84.4%). The majority of patients were symptomatic and commonest presentation was abdominal pain (76.7%). Most patients (63.2%) had comorbidities or history and hypertension and smoking were the top 2 conditions with proportion of 63.3% and 40.5% respectively. When comparing young to old patients with ICAD, no significant difference was found in demographic and clinical features including sex, comorbidities/history, and symptoms. However, we found that young patients with ICAD experienced significantly longer dissection length (SMD 1.01, 95% CI 0.16-1.86; P = .015) and distance from ostium (SMD 0.96, 95% CI 0.07-1.85; P = .013), but no significant difference was observed in true lumen compression (SMD -0.39, 95% CI -1.22-0.44; P = .364). In addition, our results showed that ICAD in young patients extending more to distal arteries, including common hepatic artery/hepatic artery (RR 2.04, 95% CI 1.13-3.68; P = .01), splenic artery (RR 2.36, 95% CI 1.24-4.49; P = .017) and left gastric artery (RR 25.42; 95% CI 1.55-417.74; P = .04). CONCLUSIONS: Though spontaneous ICAD had multitudinous clinic-pathologic features, it was apt to middle-aged males and symptomatic and abdominal pain was always the commonest presentation. Hypertension and smoking were the top 2 conditions of ICAD patients. There was significant difference between young and old patients in radiographic characteristics of ICAD which may lead to different treatment and outcomes.

The Preparation and Execution of Exploratory Human Studies on Novel 99mTc-Labeled Glucosamine Derivatives Containing Different Phenyl Isonitriles as Promising Tumor Imaging Agents.

As the "molecule of the century", 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is a radioactive 18F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [18F]FDG. In our previous work, [99mTc]Tc-CN5DG and [99mTc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images. However, they still have the disadvantage of low tumor uptake and/or high uptake by nontarget organs. To develop novel tumor imaging agents with high tumor uptake and excellent tumor/nontarget ratios, in this study, starting from d-glucosamine hydrochloride, four phenyl group-containing isonitrile ligands were designed, synthesized, and radiolabeled with 99mTc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [99mTc]Tc-L4 (i.e., [99mTc]Tc-CNMBDG) had the highest tumor uptake and tumor/background ratios among the four probes. In SPECT imaging studies, the tumor detected by [99mTc]Tc-L4 was more clearly visible than that of [99mTc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [99mTc]Tc-L4 have been conducted and successfully showed the lesion location in a patient with non-small-cell lung cancer. In summary, [99mTc]Tc-L4 is expected to be a promising tumor SPECT imaging agent.

Increased 68 Ga-FAPI Activity in Primary Small Cell Neuroendocrine Carcinoma of the Gallbladder.

ABSTRACT: Primary small cell neuroendocrine carcinomas are extremely rare heterogeneous neoplasms. We present 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of small cell neuroendocrine carcinoma of the gallbladder in a 57-year-old woman. This rare gallbladder small cell neuroendocrine carcinoma demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This demonstrates the potential value of 68 Ga-FAPI PET/CT for evaluation of gallbladder small cell neuroendocrine carcinoma.

Increased 68 Ga-FAPI Activity in Hepatic Inflammatory Myofibroblastoma.

ABSTRACT: Hepatic inflammatory myofibroblastoma is an uncommon borderline tumor. We present 68 Ga-FAPI PET/CT findings of hepatic inflammatory myofibroblastoma in a 58-year-old man. The rare hepatic inflammatory myofibroblastoma demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This case demonstrates the potential value of 68 Ga-FAPI PET/CT for the evaluation of hepatic inflammatory myofibroblastoma.

Multidisciplinary team diagnosis and treatment of pancreatic cancer: Current landscape and future prospects.

The pathogenesis of pancreatic cancer has not been completely clear, there is no highly sensitive and specific detection method, so early diagnosis is very difficult. Despite the rapid development of tumor diagnosis and treatment, it is difficult to break through in the short term and the overall 5-year survival rate of pancreatic cancer is less than 8%. In the face of the increasing incidence of pancreatic cancer, in addition to strengthening basic research, exploring its etiology and pathogenesis, it is urgent to optimize the existing diagnosis and treatment methods through standard multidisciplinary team (MDT), and formulate personalized treatment plan to achieve the purpose of improving the curative effect. However, there are some problems in MDT, such as insufficient understanding and enthusiasm of some doctors, failure to operate MDT according to the system, lack of good communication between domestic and foreign peers, and lack of attention in personnel training and talent echelon construction. It is expected to protect the rights and interests of doctors in the future and ensure the continuous operation of MDT. To strengthen the research on the diagnosis and treatment of pancreatic cancer, MDT can try the Internet +MDT mode to improve the efficiency of MDT.

In vitro and in vivo Evaluation of Folic Acid Modified DOX-Loaded 32P-nHA Nanoparticles in Prostate Cancer Therapy.

Background: Prostate cancer (PCa) ranks second in the incidence of all malignancies in male worldwide. The presence of multi-organ metastases and tumor heterogeneity often leads to unsatisfactory outcomes of conventional radiotherapy treatments. This study aimed to develop a novel folate-targeted nanohydroxyapatite (nHA) coupling to deliver adriamycin (Doxorubicin, DOX), 32P, and 99mTc simultaneously for the diagnosis and treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer. Methods: The spherical nHA was prepared by the biomimetic method and characterized. Folic acid (FA) was coupled to nHA with polyethylene glycol (PEG), and the grafting ratio of PEG-nHA and FA-PEG-nHA was determined by the thermogravimetric analysis (TGA) method. In addition, 32P, 99mTc, and DOX were loaded on nHA by physisorption. And the labeling rate and stability of radionuclides were measured by a γ-counter. The loading and release of DOX at different pH were determined by the dialysis method. Targeting of FA-PEG-nHA loaded with 99mTc was verified by in vivo SPECT imaging. In vitro anti-tumor effect of 32P/DOX-FA-PEG-nHA was assessed with apoptosis assay. The safety of the nano-drugs was verified by histopathological analysis. Results: The SEM images showed that the synthesized nHA was spherical with uniform particle size (average diameter of about 100nm). The grafting ratio is about 10% for PEG and about 20% for FA. The drug loading and the delayed release of DOX at different pH confirmed its long-term therapeutic ability. The labeling of 32P and 99mTc was stable and the labeling rate was great. SPECT showed that FA-PEG-nHA showed well in vivo tumor targeting and less damage to normal tissues. Conclusion: FA-targeted nHA loaded with 32P, 99mTc, and DOX may be a new diagnostic and therapeutic strategy for targeting PSMA-positive prostate cancer tumors, which may achieve better therapeutic results while circumventing the severe toxic side effects of conventional chemotherapeutic agents.

Pancreatic Perivascular Epithelioid Cell Tumor Revealed by 68 Ga-DOTATATE PET/CT.

ABSTRACT: We report 68 Ga-DOTATATE PET/CT findings of pancreatic perivascular epithelioid cell tumor in a 55-year-old woman. 68 Ga-DOTATATE PET/CT showed increased radioactivity in the region of pancreatic body, which suggested malignant tumor. However, postoperative pathological findings demonstrated the presence of perivascular epithelioid cell tumor. This case emphasizes the need to increase awareness of this tumor in the differential diagnosis of pancreatic nodules with moderate DOTATATE activity.

Kynurenic acid blunts A1 astrocyte activation against neurodegeneration in HIV-associated neurocognitive disorders.

Despite extensive astrocyte activation in patients suffering from HIV-associated neurocognitive disorders (HAND), little is known about the contribution of astrocytes to HAND neuropathology. Here, we report that the robust activation of neurotoxic astrocytes (A1 astrocytes) in the CNS promotes neuron damage and cognitive deficits in HIV-1 gp120 transgenic mice. Notably, knockout of α7 nicotinic acetylcholine receptors (α7nAChR) blunted A1 astrocyte responses, ultimately facilitating neuronal and cognitive improvement in the gp120tg mice. Furthermore, we provide evidence that Kynurenic acid (KYNA), a tryptophan metabolite with α7nAChR inhibitory properties, attenuates gp120-induced A1 astrocyte formation through the blockade of α7nAChR/JAK2/STAT3 signaling activation. Meanwhile, compared with gp120tg mice, mice fed with tryptophan showed dramatic improvement in cognitive performance, which was related to the inhibition of A1 astrocyte responses. These initial and determinant findings mark a turning point in our understanding of the role of α7nAChR in gp120-mediated A1 astrocyte activation, opening up new opportunities to control neurotoxic astrocyte generation through KYNA and tryptophan administration.

Clinical value of 18F-FDG PET/CT in the management of HIV-associated lymphoma.

HIV is still a major public health problem. At present, HIV-associated lymphoma remains the leading cause of deaths among people living with HIV, which should be paid more attention to. 18F-fluorodeoxglucose (FDG) PET/CT has been recommended in the initial staging, restaging, response assessment and prognostic prediction of lymphomas in general population. HIV-associated lymphoma is, however, a different entity from lymphoma in HIV-negative with a poorer prognosis. The ability to accurately risk-stratify HIV-infected patients with lymphoma will help guide treatment strategy and improve the prognosis. In the review, the current clinical applications of 18F-FDG PET/CT in HIV-associated lymphoma will be discussed, such as diagnosis, initial staging, response evaluation, prognostic prediction, PET-guided radiotherapy decision, and surveillance for recurrence. Moreover, future perspectives will also be presented.

Design and evaluation of 32P-labeled hydroxyapatite nanoparticles for bone tumor therapy.

The clinical diagnosis and treatment of malignant bone tumors are still major clinical challenges due to their high incidence are difficulty. Targeted therapies have become a critical approach to treat bone tumors. In recent years, radiopharmaceuticals have been used widely and have shown potent and efficient results in treating bone tumors, among which 32P and the labeled radiopharmaceuticals play an essential role. In this study, the 32P-labeled hydroxyapatite (HA) was prepared through chemical synthesis (32P-Hap) and physical adsorption (32P-doped-Hap). The in vitro stability of 32P-labeled HA was analyzed to assess the superiority of the new-found chemical synthesis. The radiolabeling yield and stability of chemical synthesis (97.6 ± 0.5%) were significantly improved compared with physical adsorption (92.7 ± 0.4%). Furthermore, the CT results corroborate that 32P-Hap (100 µCi) +DOX group has the highest tumor suppression rate and can effectively reduce bone destruction. The results corroborate the effectiveness of the chemical synthesis and validate the application of 32P-Hap in bone tumors. Therefore, 32P-Hap (100 µCi) + DOX may be an effective strategy for bone metastasis treatments.

Prognostic role of pretreatment 18F-FDG PET/CT and hematological parameters in relapsed/refractory Hodgkin lymphoma patients treated with immune checkpoint inhibitors and chemotherapy: a dual-center cohort study.

BACKGROUND: The combination of anti-programmed death-1 antibodies and chemotherapy is effective; however, there are no reliable outcome prediction factors. We investigated the prognostic factors based on 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) quantitative and hematological parameters to predict progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients treated with immune checkpoint inhibitors (ICIs) and chemotherapy. METHODS: This retrospective study included 31 patients who underwent 18F-FDG PET/CT before and during treatment. Pretreatment metabolic and hematological parameters were evaluated using Cox regression analysis to identify predictors of PFS. Based on the cut-off values calculated using the receiver operating characteristic (ROC) curve, patients were classified into low-, intermediate-, and high-risk groups. Kaplan-Meier curves and the log-rank test were used to compare survival differences between the groups. RESULTS: Cox multivariable analysis indicted that the treatment response based on Lactate dehydrogenase (LDH), Lugano classification and SUVmax were independent predictors of PFS (P = 0.004, 0.007 and 0.039, respectively). The optimal cut-off values for SUVmax and LDH were 11.62 and 258.5 U/L, respectively (P < 0.01). Survival curves showed that LDH ≥ 258.5U/L and SUVmax ≥ 11.62 were correlated to shorter PFS (P < 0.001, P = 0.003, respectively). The differences in PFS between the low-, intermediate-, and high-risk groups were statistically significant (P = 0.0043). CONCLUSION: In R/R cHL patients treated with ICIs and chemotherapy, Lugano classification, SUVmax, and LDH were significantly correlated with PFS. The combination of metabolic and hematological parameters predicts PFS and may help to improve patient selection.