Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics.@*METHODS@#Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve.@*RESULTS@#The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis.@*CONCLUSION@#High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

Diagnostic value of 18F-FDG PET/CT and tumor markers (CEA, CA19-9, CA24-2) in recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value of 18F-FDG PET/CT and tumor markers (CEA,CA19-9,CA24-2) in detection for recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma.@*METHODS@#Fifty-five patients were enrolled in this study. All of the patients were tested with serum CEA within 2 weeks when they underwent 18F-FDG PET/CT scan, and some patients were tested with serum CA19-9 and CA24-2 simultaneously. According to the pathology and clinical results of their follow-up, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT and tumor markers were calculated based on different divided groups, respectively.@*RESULTS@#According to the pathology and the results of their clinical follow-up, the sensitivity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 68.09%, 28.57%, 40.00% and 74.47%, respectively. The specificity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 50.00%, 66.67%, 71.43% and 50.00%, respectively. The positive predictive valueof 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 88.89%, 85.71%, 88.89% and 89.74%, respectively. The negative predictive value of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 26.67%, 11.42%, 17.24%, 25.00%, respectively. The accuracy of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 92.73%, 65.47%, 32.65%, 44.68% and 70.91%, respectively. There were 2 cases of false positive and 2 cases of false negative in 18F-FDG PET/CT.@*CONCLUSION@#18F-FDG PET/CT has high value in detecting recurrence and metastasis of postoperative colorectal carcinoma. Tumor markers have the positive value to imply the recurrence and metastasis of postoperative colorectal carcinoma and are useful to indicate when to perform the 18F-FDG PET/CT. The combination of tumor markers could improve the diagnostic efficiency to some extent.

In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting microRNA-155 in mice models / 北京大学学报(医学版)

OBJECTIVE@#MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer.@*METHODS@#Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors.@*RESULTS@#99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR.@*CONCLUSION@#99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.

Radiolabeling LyP-1 peptide and preliminary biodistribution evaluation in mice bearing MDA-MB-435 xenografts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na(131)I labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis.</p><p><b>METHODS</b>The 10-mer cyclic peptide contained the LyP-1 sequence (YCGNKRTRGC) was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na(131)I using the chloramine-T method. The [(131)I] LyP-1 peptide and a [(131)I] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained.</p><p><b>RESULTS</b>The labeling efficiencies of LyP-1 peptide reached 80% ± 5% (n = 5). The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37°C. In the biodistribution studies, the [(131)I] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [(131)I] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts.</p><p><b>CONCLUSIONS</b>The LyP-1 peptide could be effectively labeled with Na(131)I and the labeled compound is stable in human serum at 37°C for 24 hours. The high specificity of [(131)I] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.</p>

99Tcm-MDP whole body bone imaging in 25 patients with SAPHO syndrome / 中华核医学杂志

Objective To investigate the usefulness of 99Tcm-MDP whole body bone scintigraphy (WBBS) in patients with synovitis,acne,pustulosis,hyperostosis,osteitis (SAPHO) syndrome.Methods 99Tcm- MDP WBBS was performed in 25 patients (6 males,19 females,mean age =(55.1 ±9.8) years)with SAPHO syndrome.Bone lesions were classified into five categories:anterior chest wall,spine,mandible,sacroiliac joint,and limbs.The typical scintigraphic manifestations of SAPHO syndrome were summarized and compared to other radiological imaging data.Results Among 25 patients,32％ of cases (8/25)were associated with skin lesion; 48％ ( 12/25 ) were pathologically diagnosed with chronic nonspecific bone inflammation by bone biopsy.On 99Tcm-MDP WBBS,abnormal metabolic foci at anterior chest wall were found in all cases,most of which located in the sternocostoclavicular region (96％,24/25 ),including sternoclavicular joints (60％,15/25),first costosternal junctions (48％,12/25),and manubriosternal junctions (44％,11/25 ).Only 20％ of the patients (5/25) demonstrated the typical scintigraphic characteristic:“bull's head” sign.The second most frequent part was spine (44％,11/25).Appendicular skeleton was affected in 16％ (4/25) patients.WBBS also demonstrated additional skeletal lesions in 68％ (17/25 ) of the patients,mainly in first costosternal junctions (7 patients),sternoclavicular joints (6 patients),manubriosternal junctions (5 patients) and spine (4 patients).Conclusions Abnormal metabolic foci in sternocostoclavicular region and other imaging manifestations on 99Tcm- MDP WBBS can be used to diagnose,differentiate,and localize the insidious lesion and evaluate the lesion activity in patients with SAPHO syndrome.

Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma / 北京大学学报(医学版)

Objective:To investigate the possibility of using radioiodine labeled framework region(FR)antisense oligonucleotides(ASONs)as an imaging agent or antisense therapeutic radiopharmaceu-tical in lymphoma.Methods:A 18-mer partial phosphorothioate oligonucleotide sequence was synthe-sized and grafted in 5'with a tyramine group which was further radioiodinated.Radioiodination of the tyra-mine derivatized oligonucleotides was performed using the chloramine T method.(1)Normal CD-1 micewere injected via a tail vein with 148 kBq (125)~I-FR-ASON(2-3?g).Animals were sacrificed at the endof 1,2,4 and 24h,and tissue samples were studied.(2)Liposome-mediated 3.33 MBq (131)I-FR-ASON(7-9?g)were injected intralumorally into tumor-bearing BALB/c mice(6 weeks after innculation of10~7 Namalwa cells)meanwhile liposome-mediated (131)~I labeled sense oligonucleotides served as controls.Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24h afterinjection.Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios(T/NT)were calculated tot each group of mice and the difference between two groups was assessed.Results:The5′tyramine group allowed specific and stable radinlabeling of the ASON with radioiodine.The radioactivi-ty reached its peak 1h after injection,and then decreased rapidly in normal mice after intravenous ad-ministration of (125)~I-FR-ASON.The liver,stomach and intestine played an important role in biodistributionand radioactivity counts were low in bone,brain and blood.When (131)I-FR-ASON was injected intratumor-ally into mice grafted with Namalwa cell line,images showed the tracer accumulated in the tumor,Imme-diately after intratumoral administration,only the tumor was visible.Scintiscans performed at the end of 1and 2h showed elimination of the tracer from the tumor to the abdomen and at the end of 24h the tumorwas clearly seen.Percentage of the injected dose per gram of tumor and T/NT ratios for the sense group(control)were significantly lower than those of the antisense group.Conclusion:Radiolabeled Ig FRASON showed high specificity in V1 family B-cell lymphoma,which should be further investigated for nu-clear medicine imaging application and radionuclide antisense therapy.

comparative study of samarium-153-ethylenediaminetertramethylene phosphoric acid with pamidronate disodium in the treatment of patients with painful metastatic bone cancer

To assess the therapeutic efficacy and toxicity of samarium-153-ethylenediaminetetramethylene phosphonic acid [153Sm-EDTMP] and pamidronate disodium in patients with painful metastatic bone cancer. Subjects and Eighteen patients with histopathologically confirmed malignancy and multifocal bone metastases were randomized into two equal groups of 9 patients each. Group A was treated with 153Sm-EDTMP, while group B was treated with pamidronate disodium. The pain score for each patient was recorded before and after therapy using visual analogue scales that graded both the intensity and frequency of the bone pain. Therapeutic response was classified as inefficient, mild, effective and excellent. Pain score in each group prior to therapy was more than 6. In group A, 2 [22.2%] and 7 [77.8%] cases showed mild and effective response, respectively. The therapeutic efficacy of 153Sm-EDTMP was adjudged to be 77.8%. Transient myelosuppression was generally mild and reversible with white blood cells and platelets recovering after 6 weeks. In group B, palliative response in 4 cases [44.4%] was inefficient, in 1 case [11.1%] mild, in 3 cases [33.3%] effective and in 1 case [11.1%] excellent, with a therapeutic efficacy of 44.4% for pamidronate disodium. No hematological toxicity was noted. The data showed that the therapeutic efficacy of 153Sm-EDTPM was higher than that of pamidronate disodium [for pain relief maintained more than 3 weeks] and its incidence of blood toxicity was also higher than that of pamidronate disodium