Objective:To design and develop a molecular imaging probe of 68Ga-labeled bombesin (BBN) analogue, 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-polyethylene glycol (PEG) 4-BBN, and investigate its potential to target prostate cancer with high expression of gastrin-releasing peptide receptor (GRPR) while minimizing uptake in pancreatic tissue. Methods:Based on the amino acid sequence of BBN peptides, the precursor DOTA-PEG 4-BBN was designed and prepared, followed by labeling with 68Ga and conducting to quality control analysis. The tumor uptake of 68Ga-DOTA-PEG 4-BBN was assessed by microPET/CT imaging on tumor-bearing nude mice models with PC3 of high GRPR expression or HT29 of low GRPR expression (3 mice per group). 68Ga-DOTA-PEG 4-BBN microPET/CT imaging was also performed on 6 tumor-bearing nude mice models with PC3, among which 3 mice were treated with gastrin-releasing peptide antagonist 1 h prior to injection of the tracer (blocked group). After imaging, the ex vivo tissues of 3 PC3 tumor-bearing nude mice of the non-blocked group were examined for radioactivity counting to evaluation the biodistribution of 68Ga-DOTA-PEG 4-BBN, and the percentage injected dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used for data analysis. Results:The synthesis of 68Ga-DOTA-PEG 4-BBN took 40 min, with the radiochemical yield of 50%-60% (no decay correction) and the radiochemical purity of over 95%. After incubation in the serum at 37 ℃ for 4 h, the radiochemical purity remained more than 95%. The microPET/CT imaging results indicated that the uptake in the PC3 tumor was 3.2 times higher than the uptake in the tumor after GRPR blockade ((1.34±0.24) vs (0.42±0.03) %ID/g; t=5.47, P=0.005). After the injection of 68Ga-DOTA-PEG 4-BBN at 1 h and following imaging for 15 min, the PC3 tumor-bearing nude mice models of the non-blocked group showed that the pancreatic uptake ((0.150±0.058) %ID/g) was significantly lower than that in kidneys, lungs and liver ((9.452±0.234), (0.720±0.041), (1.572±0.213) %ID/g) with a profound statistical distinction ( t values: 11.28-53.02, all P<0.001). The tumor/pancreas uptake ratio could reach 16.92 in the tumor-bearing nude mice models with high GRPR expression. Conclusion:A novel molecular imaging probe 68Ga-DOTA-PEG 4-BBN demonstrates specific recognition of tumors with high GRPR expression while exhibiting low uptake in the pancreas, which shows its potential in prostate cancer molecular imaging.

Objective:To investigate the value of the extrahepatic bile duct and main pancreatic duct segment patterns on magnetic resonance cholangiopancreatography (MRCP) for differentiating the periampullary carcinoma (PAC).Methods:The clinicopathologic data of 125 patients with PAC who were admitted to Wuxi No.2 People’s Hospital from June 2013 to December 2021 were retrospectively analyzed, including 72 males and 53 females, aged (64.9±8.6) years. According to its anatomy, the extrahepatic bile duct (B) was divided into suprapancreatic and intrapancreatic (including ampullary) segments, and the main pancreatic duct (P) was divided into tail-body and head segments. MRCP patterns: i. the extrahepatic bile duct or main pancreatic duct visible without dilatation, ii. cutoff of the distal extrahepatic bile duct or main pancreatic duct with upstream dilatation, iii. cutoff of the intrapancreatic or head segment with upstream dilatation and remnant intrapancreatic or head segments invisible, iv. cutoff of the intrapancreatic or head segment with upstream dilatation and nondilated remnant intrapancreatic or head segments, were represented as 0, 1, 2, and 3, respectively. Segment patterns of B1/P0+ B1/P1, B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3, B3/P0, and B0/P0+ B2/P0 on MRCP were compared in PAC patients.Results:Of the 125 patients, there were 57 (45.6%) with pancreatic head carcinoma, 36 (28.8%) with ampullary carcinoma, 20 (16.0%) with distal cholangiocarcinoma, and 12 (9.6%) with periampullary duodenal carcinoma. Segment patterns of B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3 were found in 52 patients with pancreatic head carcinoma (91.2%, 52/57), with a significant difference between PAC (χ 2=110.66, P<0.001). Segment patterns of B1/P0+ B1/P1were found in 36 patients with ampullary carcinoma (100.0%, 36/36), fallowed by 11 (91.7%, 11/12) with periampullary duodenal carcinoma, with a significant difference between PAC (χ 2=129.95, P<0.001). Segment pattern of B3/P0 presented in 16 patients with distal cholangiocarcinoma (80.0%, 16/20), with a significant difference between PAC (χ 2=62.45, P<0.001). The segment patterns of B0/P0+ B2/P0 were only seen in 3 of 57(5.3%) patients with pancreatic head carcinoma. Conclusion:On MRCP, cutoff of the head segment with upstream dilatation and remnant head segment invisible or nondilated indicates the pancreatic head carcinoma. Cutoff of the intrapancreatic segment with upstream dilatation, remnant intrapancreatic segment visible, and main pancreatic duct nondilated, indicates the distal cholangiocarcinoma. And cutoff of the distal extrahepatic segment with upstream dilatation and main pancreatic duct dilatation or not, indicates the ampullary or periampullary duodenal carcinoma.

Objective:To explore the application potential of 18F-Asp-Glu-val-Asp (DEVD)-Cys(StBu)-PPG(CBT)-AmBF 3 ( 18F-1; PPG: propargyl-glycine; CBT: 2-cyanobenzothiazole; AmBF 3: ammoniomethyl-trifluoroborate) PET imaging in early monitoring of triple-negative breast cancer (TNBC) radiotherapy response. Methods:Ten MDA-MB-231 tumor bearing nude mice models were constructed and divided into radiotherapy group ( n=5) and non-radiotherapy group ( n=5) by random sampling method. The radiotherapy group was treated with single irradiation at a dose of 8 Gy. 18F-1 microPET imaging was performed in the radiotherapy and non-radiotherapy groups, and the tumor uptake and muscle uptake in 2 groups at different time points (2.5, 7.5, 12.5, 17.5, 22.5, 27.5, 32.5, 37.5, 42.5, 47.5, 52.5, 57.5 min after injection) were analyzed. The specific uptake of the probe in apoptotic cells was verified by radioautography, HE staining and immunofluorescent staining. Repeated measures analysis of variance and one-way analysis of variance were used to analyze data. Results:18F-1 microPET imaging showed that there was significant difference between tumor uptake and muscle uptake in radiotherapy group ( F=20.27, P=0.011). The uptake of radiotherapy group was the highest at 7.5 min after injection ((4.64±0.35) percentage activity of injection dose per gram of tissue(%ID/g)). There was no significant difference between tumor uptake and muscle uptake in the non-radiotherapy group ( F=1.81, P=0.215). The tumor/muscle (T/M) ratio of radiotherapy group was higher than that of non-radiotherapy group ( F=31.95, P=0.005), with the highest at 47.5 min after injection (2.49±0.46). Radioautography showed that the tumor radioactivity in radiotherapy group was higher than that of muscle in radiotherapy group, and was also higher than tumor and muscle radioactivies in non-radiotherapy group ( F=116.79, P<0.001). HE staining and immunofluorescent staining verified that 18F-1 could specifically detect the activity of caspase-3 activated in tumor cells after radiotherapy. Conclusion:18F-1 can specifically recognize the activated caspase-3 after TNBC radiotherapy, and monitor radiotherapy response at the molecular level by apoptosis PET imaging.

We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

Abstract During the yellow fever epidemic in Angola in 2016, cases of yellow fever were reported in China for the first time. The 11 cases, all Chinese nationals returning from Angola, were identified in March and April 2016, one to two weeks after the peak of the Angolan epidemic. One patient died; the other 10 cases recovered after treatment. This paper reviews the epidemiological characteristics of the 11 yellow fever cases imported into China. It examines case detection and disease control and surveillance, and presents recommendations for further action to prevent additional importation of yellow fever into China.

Objective:To investigate the clinical application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in preoperative evaluation of adjacent organ invasion for periampullary carcinomas (PACs).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 81 patients with PACs who were admitted to the Affiliated Wuxi No.2 People′s Hospital of Nanjing Medical University from September 2013 to June 2019 were collected. There were 52 males and 29 females, aged from 41 to 80 years, with an average age of 62 years. Observation indicators: (1) surgical and pathological outcomes; (2) evaluation of adjacent organ invasion on CT and MRI examination for PACs; (3) comparison of diagnostic accuracy between CT and MRI examination in assessing adjacent organ invasion for PACs; (4) auxiliary and feature images of adjacent organ invasion for PACs; (5) comparison between CT and MRI examination in assessing adjacent organ invasion for PACs. Measurement data with skewed distribution were represented as M (range), and count data were described as absolute numbers or percentages. Comparison between groups was analyzed using the Mann-Whitney U test.The receiver operating characteristic curve and area under curve were used to evaluate diagnostic accuracy between CT and MRI examination in assessing adjacent organ invasion for PACs. Consistency was compared using the κ test. Results:(1) Surgical and pathological outcomes: of the 81 patients, 76 underwent pancreatoduodenectomy, 5 underwent palliative gastrojejunostomy or biliary drainage combined with biopsy, including the pancreas, duodenum, or lymph nodes. Of the 81 patients, 35 had pancreatic head carcinoma including 26 with duodenal invasion and 9 without duodenal invasion; 23 had ampullary carcinoma including 17 with duodenal invasion, 4 with both duodenal invasion and pancreatic invasion, and 2 without duodenal invasion or pancreatic invasion; 17 had distal bile duct carcinoma (including papillary type in 4 patients and periductal infiltrative type in 13 patients), of which 8 had duodenal invasion, 1 had duodenal invasion and pancreatic invasion (pathological classification of the 9 patients was periductal infiltrative type), 8 had neither duodenal invasion nor pancreatic invasion; 6 had duodenal carcinoma including 4 with pancreatic invasion and 2 without pancreatic invasion. (2) Evaluation of adjacent organ invasion on CT and MRI examination for PACs: of the 35 patients with pancreatic head carcinoma, duodenal invasion was identified in 25 patients and no duodenal invasion in 10 patients on both CT and MRI examination. Of the 23 patients with ampullary carcinoma, duodenal invasion, pancreatic invasion, both duodenal invasion and pancreatic invasion, and neither duodenal invasion nor pancreatic invasion were identified in 17, 1, 4, and 1 patients on CT examination, respectively; the above indicators were identified in 15, 2, 4, and 2 patients on MRI examination. Of the 17 patients with distal bile duct carcinoma, pancreatic invasion, both duodenal invasion and pancreatic invasion, and neither duodenal invasion nor pancreatic invasion were identified in 8, 1, and 8 patients on CT examination, respectively; the above indicators were identified in 9, 1, and 7 patients on MRI examination. Of the 6 patients with duodenal carcinoma, pancreatic invasion and no pancreatic invasion were identified in 3 and 3 patients on both CT and MRI examination.(3) Comparison of diagnostic accuracy between CT and MRI examination in assessing adjacent organ invasion for PACs: two reviewers had good agreement in assessing adjacent organ invasion on CT examination for pancreatic head carcinoma, ampullary carcinoma, and distal bile duct carcinoma ( κ=0.868, 0.701, 0.881, P<0.05), but they had poor agreement for duodenal carcinoma ( κ=0.333, P>0.05). Meanwhile, two reviewers had good agreement in assessing adjacent organ invasion on MRI examination for pancreatic head carcinoma and ampullary carcinoma( κ=0.860, 0.747, P<0.05), and moderate agreement for distal bile duct carcinoma ( κ=0.643, P<0.05), but they had poor agreement for duodenal carcinoma ( κ=0.333, P>0.05). (4) Auxiliary and feature images of adjacent organ invasion for PACs: for the 25 patients who had pancreatic head carcinoma with duodenal invasion on CT and MRI examination, based on well filling in duodenum, 12 patients showed locally morphological change of lumen and flattened or disappeared duodenal mucosal folds on negative contrast CT cholangiopancreatography; 14 patients showed similar signs on T2 weighted imaging or magnetic resonance cholangiopancreatography. The 17 patients who had distal bile duct carcinoma with pancreatic invasion on CT and MRI examination were periductal infiltrative type. Pancreatic invasion manifested as local thickenness of ductal wall with marked enhancement and narrowed ductal lumen, which was indistinguishable from the pancreas, and the pancreatic parenchyma showed hyperdense or hyperintense signs similar with the lesion, like a "transmural" sign. One patient with both duodenal invasion and pancreatic invasion showed locally thickened and enhanced duodenal wall on both CT and MRI examination. Four patients, who had papillary type distal bile duct carcinoma with neither duodenal invasion nor pancreatic invasion, showed intraductal growing mass which had a discernible boundary to the pancreas and slighter enhancement than infiltrative type on both CT and MRI examination. (5) Comparison between CT and MRI examination in assessing adjacent organ invasion for PACs: CT examination evaluating adjacent organ invasion for pancreatic head carcinoma, ampullary carcinoma, distal bile duct carcinoma, and duodenal carcinoma had a sensibility of 92.3%, 90.5%, 88.9%, 75.0%, a specificity of 88.9%, 50.0%, 87.5%, 100.0%, an accuracy of 0.906, 0.702, 0.882, 0.875, respectively. MRI examination evaluating adjacent organ invasion for pancreatic head carcinoma, ampullary carcinoma, distal bile duct carcinoma, and duodenal carcinoma had a sensibility of 88.5%, 85.7%, 88.9%, 75.0%, a specificity of 77.8%, 50.0%, 75.0%, 100.0%, an accuracy of 0.831, 0.679, 0.819, 0.875. There was no significant difference in sensibility for pancreatic head carcinoma, distal bile duct carcinoma, or duodenal carcinoma between CT and MRI examination( χ2=3.140, 0.141, 0.444, P>0.05), while there was a significant difference in sensibility for ampullary carcinoma ( χ2=13.263, P<0.05). There was no significant difference in specificity for pancreatic head carcinoma, ampullary carcinoma, or distal bile duct carcinoma between CT and MRI examination( χ2=0.321, 2.000, 3.429, P>0.05). There was no significant difference in accuracy for pancreatic head carcinoma, ampullary carcinoma, distal bile duct carcinoma, or duodenal carcinoma between CT and MRI examination( Z=0.967, 0.273, 0.559, 0.000, P>0.05). Conclusion:CT and MRI examination can be used for preoperative evaluation of adjacent organ invasion for periampullary carcinoma, with similar performance in specificity and accuracy, however, CT examination has a higher sensibility for ampullary carcinoma.

Objective To explore the limits of fluid-inversion prepared diffusion weighted imaging (FLIPD) in detection of acute cerebral ischemic lesions.Methods From January 2012 to March 2014,forty-nine patients (33 males,16 females,age (55.6± 12.3) years) clinically diagnosed as transient ischemic attack (TIA) were included.Patients underwent brain MRI (conventional diffusion weighted imaging (DWI) and FLIPD) within 3 d after the onset of TIA.The detection ability of MRI with the two sequences was compared,and the relative signal intensity (rSI) and apparent diffusion coefficient (ADC) of acute ischemic lesions based on two sequences were compared.Kappa test and two-sample t test were used to analyze the data.Results A total of 87 acute ischemic lesions were detected in 21 patients by conventional DWI,and 54 were detected in 19 patients by FLIPD (Kappa=0.916,P＜0.05).The rSI of ischemic lesions on FLIPD was significantly lower than that on conventional DWI (1.37±0.22 vs 1.57±0.26;t=6.647,P＜0.001).The ADC value of ischemic lesions on FLIPD was slightly lower than that on conventional DWI:(0.54 ±0.10) ×10-3 mm2/s vs (0.57±0.13)×10-3 mm2/s (t=2.120,P＜0.05).The missed lesions on FLIPD were located in the white matter (n =18),cerebellum and brainstem (n =8),and the cortex (n =7).Conclusions A slight diffuse abnormality may be missed on FLIPD,so this method is not suitable for the detection of acute ischemic lesions.FLIPD technology still needs improvement.

Objective To fabricate manganese-doped carbon quantum dots(Mn-CDs)@anti-human epididymis protein 4(HE4)monoclonal antibody(Mn-CDs@Anti-HE4 mAb)dual-modal fluorescent-magnetic nanoprobe for ovarian cancer cells targeting imaging,and evaluate its potential on fluorescent imaging and MRL Methods Mn-CDs were synthesized at 150 ℃ with solvothermal method.The average diameter,fluorescent capability and MRI efficiency were determined.The cytotoxicity of Mn-CDs in vitro was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)assay with HO-8910 ovarian cancer stem cells and EA.hy926 human umbilical vein endothelial cells.Mn-CDs@Anti-HE4 mAb was fabricated with condensation reaction and characterized by ultraviolet(UV)absorption spectra.Fluorescence imaging and MRI in vitro was performed for cancer cell-targeting study.One-way analysis of variance and the least significant difference t test were used to analyze the data.Results The Mn-CDs with diameter of(4.64±0.85)nm showed a well-defined spherical morphology.The fluorescent spectra of Mn-CDs exhibited a typical excitation-dependent behavior with an excitation maximum at 360 nm and emission maximum at 440 nm.The T1 relaxation rate was(3.26±0.04)mmol ? L-1 ? s-1.The cytotoxicity tests in vitro showed that the survival rates of HO-8910 cells and EA.hy926 cells were both significantly different after treated with different concentrations of Mn-CDs(F= 1 947.509,260.174,both P<0.05),and there was no cytotoxicity in both HO-8910 cells and EA.hy926 cells at concentrations of MnCDs within 0-2.5 mg/ml(all P>0.05),while the survival rates of the two kinds of cells were descended with the increasing of concentration within 3.0-4.5 mg/ml(P<0.05).Mn-CDs@Anti-HE4 mAb could target HO-8910 cells on fluorescence imaging and MRI.Conclusions Mn-CDs@Anti-HE4 mAb,with good potential on fluorescence imaging,MRI and targeting ability,is successfully synthesized.It may provide a new method for early diagnosis of ovarian cancer.

Objective To explore the feasibility of electrocardiogram (ECG)-gated coronary artery calcium scoring (CACS) CT scan for attenuation correction of 9gTcm-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging (MPI) based on a hybrid SPECT/CT scanner.Methods From January 2017 to October 2017,a total of 110 subjects (61 males,49 females;age:(68.4±9.4) years) underwent ECG-gated MPI,ECG-gated CACS CT scan and conventional non-gated cardiac CT scan.The gated and non-gated CT scans were used for attenuation correction of MPI separately,then the relative percentage of radioactive distribution of left ventricular (LV) walls (anterior,lateral,inferior,septal and apex) based on different correction methods were compared,and the influences of CACS CT scan and conventional CT scan on visual assessment for myocardial ischemia were also compared.Paired t test and Kappa test were used to analyze the data.Results The relative radioactive distribution percentages of all LV walls in CACS CT corrected MPI and those in conventional CT corrected MPI were not statistically significant (t values:from-0.782 to 0.456,all P＞0.05).The weighted Kappa values of LV anterior,lateral,inferior,septal and apex from 2 types of corrected images between 2 physicians were 0.864 (95％ CI:0.749-0.979),0.795 (95％ CI:0.717-0.874),0.494(95％ CI:0.076-0.912),0.724(95％ CI:0.321-1.000),0.873 (95％ CI:0.764-0.982),respectively (all P＜0.01).Conclusion ECG-gated CACS CT scan can be used for attenuation correction of 99Tcm-MIBI MPI based on a hybrid SPECT/CT scanner.

Objective: To prepare manganese-doped carbon quantum dots (Mn-CDs) dual-modal nanoprobe for fluorescent-magnetic imaging, and evaluate its characteristics and potential on fluorescence imaging and MRI. Methods: Mn-CDs were synthesized at 150 ℃. The form, diameter, component, fluorescent capability, T₁ relaxation rate, stability and cytotoxicity of Mn-CDs in vivo were verified. The fluorescence imaging of HO-8910 tumor-bearing mice was performed on small animal imager, and the whole-body enhanced imaging was performed on 3.0 T MRI scanner. One-way analysis of variance was used to analyze the data. Results: The Mn-CDs with the diameter of (4.64±0.85) nm showed a well-defined spherical morphology. The fluorescent spectra of Mn-CDs exhibited that the excitation maximum was at 360 nm and the emission maximum was at 440 nm. The T₁ relaxation rate was (3.26±0.04) mmol·L^-1·s^-1. The Mn-CDs had good stability of fluorescent and magnetic imaging capability at 0, 0.25, 0.5, 0.75, 1.0 and 2 months at room temperature with no significant differences of fluorescent and magnetic signals (F=1.566 and 0.987, both P>0.05). After injection of 200 μl Mn-CDs (15 g/L), mice were all alive and had no viscera damage. The tumor could be observed obviously on fluorescence imaging at 5 min. Enhanced MRI showed that the tumor was unevenly enhanced and Mn-CDs were mainly cleared away through urinary system. Conclusion Mn-CDs are stable and have good potential on fluorescence imaging and MRI, which provides a promising multimodal imaging method for tumor detection and monitoring.