New frontiers in focal therapy for prostate cancer:Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging

Imaging has a central role in the context of focal therapy(FT)for prostate cancer(PCa).Prostate-specific membrane antigen(PSMA)positron emission tomography/magnetic resonance imaging(PET/MRI)is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET.Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios.Limited evidence on PSMA PET/MRI is available in the setting of FT.PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa.PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence.The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography.PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT.Further studies are needed to confirm its applications in this specific clinical setting.

Establishment of FAP-overexpressing Cells for FAP-targeted Theranostics

Objective Fibroblast activation protein(FAP)has been widely studied and exploited for its clinical applications.One of the difficulties in interpreting reports of FAP-targeted theranostics is due to the lack of accurate controls,making the results less specific and less confirmative.This study aimed to establish a pair of cell lines,in which one highly expresses FAP(HT1080-hFAP)and the other has no detectable FAP(HT1080-vec)as control,to accurately evaluate the specificity of the FAP-targeted theranostics in vitro and in vivo.Methods The cell lines of the experimental group(HT1080-hFAP)and no-load group(HT1080-vec)were obtained by molecular construction of the recombinant plasmid pIRES-hFAP.The expression of hFAP in HT1080 cells was detected by PCR,Western blotting and flow cytometry.CCK-8,Matrigel transwell invasion assay,scratch test,flow cytometry and immunofluorescence were used to verify the physiological function of FAP.The activities of human dipeptidyl peptidase(DPP)and human endopeptidase(EP)were detected by ELISA in HT1080-hFAP cells.PET imaging was performed in bilateral tumor-bearing nude mice models to evaluate the specificity of FAP.Results RT-PCR and Western blotting demonstrated the mRNA and protein expression of hFAP in HT1080-hFAP cells but not in HT1080-vec cells.Flow cytometry confirmed that nearly 95%of the HT1080-hFAP cells were FAP positive.The engineered hFAP on HT1080 cells had its ability to retain enzymatic activities and a variety of biological functions,including internalization,proliferation-,migration-,and invasion-promoting activities.The HT1080-hFAP xenografted tumors in nude mice bound and took up^(68)GA-FAPI-04 with superior selectivity.High image contrast and tumor-organ ratio were obtained by PET imaging.The HT1080-hFAP tumor retained the radiotracer for at least 60 min.Conclusion This pair of HT1080 cell lines was successfully established,making it feasible for accurate evaluation and visualization of therapeutic and diagnostic agents targeting the hFAP.

^(18)F-FDG PET/CT in differentiating malignant from benign origins of obstructive jaundice

BACKGROUND： The various origins of obstructive jaundice make the diagnosis of the disease difficult. This study was undertaken to evaluate the role of 18F-FDG PET/CT in differentiating malignant from benign origins of obstructive jaundice and to quantify the added value of 18F-FDG PET/CT over conventional imaging（enhanced CT and/or MRI）.METHODS： Eighty-five patients with obstructive jaundice who underwent 18F-FDG PET/CT within 2 weeks after enhanced CT and/or MRI were reviewed retrospectively. All 18F-FDG PET/CT images were independently evaluated by 2 nuclear medicine physicians who were unaware of other imaging data; differences were resolved by consensus of the physicians. All conventional imaging interpretations, according to the medical records, were reviewed by 2 radiologists to determine the potential value. Final diagnoses were based on histological or surgical findings.RESULTS： Sixty-six patients were diagnosed with malignancies, and 19 patients with benign lesions. The maximum standardized uptake values for malignant and benign lesions causing biliary obstruction were 8.2±4.4 and 4.0±5.0, respectively（P〈0.05）. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign origins with 18F-FDG PET/CT were 86.4%（57/66）, 73.7%（14/19）, and 83.5%（71/85）, respectively. 18F-FDG PET/CT in conjunction with conventional imaging changed the sensitivity, specificity, and overall accuracy of conventional imaging alone from 75.8%（50/66） to 95.5%（63/66）（P〈0.05）, 68.4%（13/19） to 57.9%（11/19）（P〉0.05）, and 74.1%（63/85） to 87.1%（74/85）（P〈0.05）, respectively.CONCLUSIONS： 18F-FDG PET/CT is of great value in differentiating malignant from benign origins of obstructive jaundice and is a useful adjuvant to conventional imaging. 18F-FDG PET/CT should be recommended for further etiological clarification.

Dynamic contrast-enhanced MRI versus ^(18)F-FDG PET/CT: Which is better in differentiation between malignant and benign solitary pulmonary nodules?

Objective： To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging（DCE-MRI） with that of^18F-fluorodeoxyglucose（^18F-FDG） positron emission tomography/computed tomography（PET/CT） in the differentiation of malignant and benign solitary pulmonary nodules（SPNs）.Methods： Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and ^18F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant（K^trans）, redistribution rate constant（Kep）, and fractional volume（Ve）, were calculated using the Extended-Tofts Linear two-compartment model. The ^18F-FDG PET/CT parameter, maximum standardized uptake value（SUV（max））, was also measured. Spearman＇s correlations were calculated between the MRI pharmacokinetic parameters and the SUV（max） of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic（ROC） analyses were used to compare the diagnostic capability between the DCE-MRI and ^18F-FDG PET/CT indexes.Results： Positive correlations were found between K^trans and SUV（max）, and between K（ep） and SUV（max）（P〈0.05）.There were significant differences between the malignant and benign nodules in terms of the K^trans, K（ep） and SUV（max） values（P〈0.05）. The areas under the ROC curve（AUC） of K^trans） K（ep） and SUV（max） between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for K^trans; 87.5% and 76.5% for K（ep）; and 75.0% and 70.6%for SUV（max）, respectively. The sensitivity and specificity of K^trans and K（ep） were higher than those of SUV（max）, but there was no significant difference between them（P〉0.05）.Conclusions： DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free.

^(18)F-FDG PET/MR Imaging for Evaluating of Obstructive Jaundice:Chinese Expert Consensus

The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)offers complementary information from PET and MR in the diagnosis of obstructive jaundice and is becoming widely adopted in clinical setting.While preserving its diagnostic accuracy,it is important to standardize and streamline the clinical scan protocol of PET/MR in evaluating obstructive jaundice.Based on literature review and experience of large number of clinical cases from the author group,this article reports an expert consensus on imaging protocol optimization and case interpretation template standardization.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury

Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanoparticles(PCurNP)are designed to meet the renal excretion threshold(~45 kDa),presenting a controllable delivery nanosystem for kidney targeting.Renal accumulation of the relatively small nanoparticles,^(89)Zr-PCurNP M10 with the diameter between 5 and 8 nm,is found to be 1.7 times and 1.8 times higher than the accumulation of^(89)Zr-PCurNP M29(20-50 nm)and M40(20-50 nm)as revealed by PET imaging.Furthermore,serum creatinine analysis,kidney tissues histology,and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI.Herein,PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.