Relationship between the SUV max of primary lesion on 18F-FAPI-42 PET/CT imaging and the clinicopathological characteristics of patients with gastric cancer / 中华核医学与分子影像杂志

Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.

Preclinical evaluation and pilot clinical study of 18FAlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel 18F-labeled FAP tracer ([18F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [18F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [18F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [18F]FAPI-42, [18F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [18F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [18F]FAPI-42 (3.2 ± 0.6% ID/g) and [68Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [18F]AlF-P-FAPI and [18F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [18F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.

Efficient lung cancer-targeted drug delivery a nanoparticle/MSC system

Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.

Establishment of a diagnostic model for charactering solitary pulmonary nodule based on 18F-FDGPET/CT and clinical data / 中华核医学与分子影像杂志

Objective To establish a diagnostic model based on 18F-FDG PET/CT and clinical data and assess its diagnostic potency for characterizing SPN.Methods From November 2004 to May 2014,164 patients with SPN who underwent 18F-FDG PET/CT scan were retrospectively analyzed.The patients'clinical factors (age,gender,history of smoking and history of malignancy),information on CT (diameter,location and spiculated edge of the lesion) and metabolic information on PET imaging were collected to establish a diagnostic model by using the binary logistic regression.Then,the optimal operating point (OOP)of the established model was set.The diagnostic potencies of the established model and PET were assessed by ROC curve.Results Malignancy was diagnosed in 104 of 164 SPN patients.The rest 60 patients had benign diseases.The factors of age,spiculation(0:no spiculation,1:obvious spiculation) and metabolic information(0:≤ mediastinal blood pool,1:＞mediastinal blood pool) were demonstrated to be useful for the establishment of the model (x2 =5.486,16.240,33.855,all P＜0.05).However,the factors of gender,history of smoking,the diameter and location of lesions showed no influence for the model (x2 =2.452,0.453,0.127,0.390,all P＞0.05) and rejected from the model established.The history of malignancy was excluded from statistical analysis because there were only 2 patients with history of malignancy.The established model was as follows:P=1/(1+e-Z),z=-5.512+0.061xage+2.208xspiculation+3.767×metabolic increase.The ROC AUC of the established model and PET using two-point scoring scale (TPSS) for charactering SPN were 0.92(95％ CI:0.87-0.96)and 0.80(95％ CI:0.73-0.86).The model had higher diagnostic efficacy compared with TPSS (z=4.369,P＜0.05).When P=0.796 7 was set as an OOP,the diagnostic sensitivities of the model and PET for charactering SPN were 91.3％ (95/104) and 94.2％ (98/104) respectively,and no significant difference was found between them (x2 =0.800,P＞0.05).However,significant difference was found between the diagnostic specificities of them (80.0％ (48/60) vs 65.0％ (39/60);x2 =7.111,P＜0.05).Conclusions A new diagnostic model for characterizing SPN based on the information from 18FFDG PET,thin-section CT and clinical data is successfully established.Its sensitivity for diagnosis of lung cancer is high,and its specificity is superior to PET using with TPSS.This model has a potential value for clinical application.

Value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients with recurrent uterine cervical cancer / 中华核医学与分子影像杂志

Objective To investigate the value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients.with recurrent uterine cervical cancer.Methods Forty-five patients with recurrent uterine cervical cancer underwent 18F-FDG PET/CT before and after treatment from October 2004 to December 2014,and their PET/CT results were retrospectively analyzed.Treatment response was categorized as complete metabolic response (CMR),partial metabolic response (PMR),stable metabolic disease (SMD) and progressive metabolic disease (PMD) according to PET response criteria in solid tumors (PERCIST).Kaplan-Meier survival analysis was used.The difference of progression-free survival (PFS) between patients with and without PMD was compared by x2 test.The PFS difference among patients with different SUVmax on pretreatment PET/CT was also compared byx2 test.Results After treatment,22.2％ (10/45) of patients were categorized as CMR,22.2％(10/45) as PMR,4.4％(2/45) as SMD and 51.1％ (23/45) as PMD by post-treatment 18F-FDG PET/CT.Thirty-two patients had long-term (6-64 months) clinical follow-up.The PFS was 1-64 months and the median PFS was 5 months.The patients without PMD had a significantly better PFS than those with PMD(12.2 vs 4.2 months,x2 =7.223,P＜0.01).Patients with lesion SUVmax＜7.5 on pretreatment PET/CT had a better PFS than those with SUVmax ≥7.5 (16.3 vs 5.9 months,x2 =5.415,P＜0.05).Conclusion 18F-FDG PET/CT is useful forthe evaluation of treatment response and prognosis in patients with recurrent cancer of the uterine cervix.

Preliminary study on the evaluation of Langerhans cell histiocytosis using F-18-fluoro-deoxy-glucose PET/CT / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG PET/CT) in Langerhans cell histiocytosis (LCH). The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH.</p><p><b>METHODS</b>Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans. The diagnosis of LCH was established by pathology, multi-modality imaging, and clinical follow-up.</p><p><b>RESULTS</b>F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive. All 45 LCH lesions were F-18-FDG avid including six small bone lesions <1.0 cm in diameter. The mean maximal standardized uptake value (SUVmax) was 7.13 ± 4.91. F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions (SUVmax: 6.50 ± 2.97 vs. 7.93 ± 6.60, t = -0.901, P = 0.376). Among 45 LCH lesions, 68.9% (31/45) were found in bones and 31.1% (14/45) in soft tissue. The most commonly involved bones were the pelvis and vertebrae. There was no significant difference in F-18-FDG uptake between bone lesions vs. non-bone lesions (SUVmax: 6.30 ± 2.87 vs. 8.97 ± 7.58, t = 1.277, P = 0.221). In two patients, changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment.</p><p><b>CONCLUSIONS</b>The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH. Because of the small sample size, further research is warranted to confirm our findings.</p>

Tumor targeting efficacy of a novel PET radiotracer (1)8F-AlF-NOTA-PRGD2 in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the tumor targeting efficacy of (18)F-AlF-NOTA-PRGD2, a novel radiotracer of Arginine-glycine-aspartic acid (RGD) peptides.</p><p><b>METHODS</b>(18)F-AlF-NOTA-PRGD2 was synthesized in one-step by conjugating NOTA-PRGD2 with (18)F-AlF at 100 degrees celsius;. The tumor targeting efficacy and in vivo biodistribution profile of (18)F-AlF-NOTA-PRGD2, following intravenous injection via the tail vein, were evaluated in a nude mouse model bearing subcutaneous U87MG glioblastoma xenograft by radioactivity biodistribution assessment, PET/CT and microPET/CT.</p><p><b>RESULTS</b>NOTA-PRGD2 was (18)F-fluorinated successfully in one-step with a yield of 17%-25% within 15-20 min. Radioactivity biodistribution study confirmed the tumor-targeting ability of (18)F-AlF-NOTA-PRGD2 in the tumor-bearing mice. At 1 and 2 h following injection, (18)F-AlF-NOTA-PRGD2 uptake in the tumor reached 4.14∓1.44 and 2.80∓1.18 % ID/g (t=1.910, P=0.070) with tumor/brain ratios of 2.95∓0.61 and 5.21∓2.62, respectively (t=-1.686, P=0.167). Both PET/CT and microPET/CT were capable of showing the radioactivity biodistribution of (18)F-AlF-NOTA-PRGD2 in the mouse model and clearly displayed the tumor, but microPET/CT showed a much better image quality.</p><p><b>CONCLUSION</b>(18)F-AlF-NOTA-PRGD2 prepared by one-step radiosynthesis can selectively target to the tumor, demonstrating its potential as a good radiotracer for tumor imaging.</p>

Value of the dual phase 18F-FDG PET/CT in the diagnosis of recurrent and metastatic bladder cancer after surgery / 实用医学杂志

Objective To investigate the clinical value of dual phase 18F-FDG PET/CT in the diagnosis of recurrent and metastatic bladder cancer after surgery. Methods The imaging data from 84 patients underwent the dual phase 18F-FDG PET/CT after surgery with known histories of bladder cancer were analyzed. Among the 84 patients, 16 had symptoms of recurrence, 24 had symptoms of metastasis and 44 didn′t have any symptom. The median interval time between the primary tumor resection and the PET/CT scan was 11.5 months (0.5 ~ 240 months). According to the PET/CT imaging procedures, all patients underwent whole body PET/CT scan at 60 minutes after IV injection of 18F-FDG. Additional delayed pelvic PET/CT images were acquired after forced diuresis by using oral 40 mg furosemide. The 18F-FDG PET/CT findings were compared with histopathologic examination results and (or) the clinical follow-up. All patients were followed up for more than six months. Results Results of detecting recurrence and metastasis of bladder cancer showed that the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the dual phase FDG PET/CT imaging protocol were 91.7%(22/24), 95.0%(57/60), 94.0%(79/84), 88.0%(22/25), 96.6%(57/59) and 90.0%(27/30), 96.3%(52/54), 94.0%(79/84), 93.1%(27/29), 94.5%(52/55), respectively. Conclusion Dual phase FDG PET/CT can be used to detect the recurrence and metastasis with high accuracy, contributing to the restaging and follow-up in bladder cancer after surgery.

Value of dual-phase (18)F-FDG PET/CT in preoperative staging of bladder cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical value of dual-phase (18)F-FDG PET/CT with oral diuretics in preoperative staging of bladder cancer.</p><p><b>METHODS</b>The imaging data were analyzed of 73 patients with bladder cancer undergoing preoperative dual-phase (18)F-FDG PET/CT with oral diuretic between May, 2003 and May, 2012. All the patients underwent whole-body PET/CT scan 60 min after intravenous injection of 270-350 MBq of (18)F-FDG. Additional delayed pelvic PET/CT images were acquired after forced diuresis using oral furosemide (40 mg). All the patients underwent subsequent radical cystectomy, and (18)F-FDG PET/CT findings were compared with the histopathologic results to evaluate the value of dual-phase (18)F-FDG PET/CT in preoperative staging.</p><p><b>RESULTS</b>The concordance rate of dual-phase FDG PET/CT-based bladder cancer staging with the histopathologic results was 63.0% in the 73 patients, and was 100% (7/7) for pT4 bladder cancers. With dual-phase FDG PET/CT, the detection rate was 75.0% (6/8) for lymph node metastases, 100% (4/4) for distant metastases, and 100% (4/4) for other concurrent primary malignancies.</p><p><b>CONCLUSION</b>Though with limited accuracy in T-staging of pTa, pT1, pT2, and pT3 bladder cancer, dual-phase FDG PET/CT has important clinical value in staging of pT4 bladder cancer and in N-staging, M-staging and detection of other concurrent primary malignancies.</p>

Complementary value of 11C-choline PET/CT to 18F-FDG PET/CT for diagnosing nasopharyngeal and hepatocellular carcinoma / 中华核医学与分子影像杂志

Objective To evaluate the complementary value of 11C-choline (CHO) PET/CT to 18F-FDG PET/CT in the staging of locally advanced nasopharyngeal carcinoma (NPC) and diagnosis of HCC.Methods From December 2007 to January 2010,15 patients with locally advanced NPC and 76 patients with HCC were prospectively enrolled into this study.The research was approved by the ethics committee,and all patients signed informed consents.Whole body 18 F-FDG PET/CT scans were performed on all patients and regional 11C-CHO PET/CT was conducted in 43 patients (15 with NPC,28 with HCC).A lesion with increased uptake of either 11 C-CHO or 18F-FDG was considered positive.SUVmax,tumor/brain (T/B) ratio and tumor/liver (T/L) ratio were calculated for semi-quantitative analysis.Two-sample t test,x2 test,Fisher exact test and linear correlation analysis were used for statistical analysis.Results (1) The lesion SUVmax of 18 F-FDG was higher compared to 11C-CHO (12.81 ± 5.00 vs 6.84 ± 2.76 ; t =6.416,P ＜0.01) in NPC patients.However,11C-CHO PET/CT had a much higher T/B ratio than 18F-FDG (18.62 ±7.95 vs 1.38 ±0.59 ; t =8.801,P ＜ 0.01).Significant correlation was found between the 2 tracers with regard to NPC lesion uptake (r =0.712,P ＜0.01).Compared with 18F-FDG PET/CT,11C-CHO PET/CT had better delineation of intracranial invasion in 50.0％ of patients (12/12 vs 6/12; x2 =8.000,P ＜0.05),skull base invasion in 4/14 patients and orbital invasion in 3/3 patients.(2) 18F-FDG PET/CT showed positive findings in 63.1％ (48/76) of HCC patients.In 28 HCC patients with negative findings on 18F-FDG PET/CT,11 C-CHO PET/CT was positive in 71.4％ (20/28) of patients.The dual-tracer PET/CT improved the diagnostic sensitivity (89.5％,68/76) of HCC compared with 18F-FDG PET/CT (63.1％,48/76) alone (x2 =14.559,P ＜0.01).11C-CHO PET/CT was more sensitive than 18F-FDG PET/CT for the detection of well differentiated HCC (6/9 vs 35.7％ (5/14) ; P =0.214).For the detection of moderately differentiated HCC,the sensitivity of 11C-CHO and 18F-FDG PET/CT was similar to each other (6/7vs 72.0％ (18/25),P =0.648).11C-CHO PET/CT was more sensitive than 18F-FDG for the detection of HCC lesions ＜5.0 cm (72.7％ (16/22) vs 42.1％ (16/38) ; x2 =5.249,P ＜0.05),especially for lesions ＜ 2.0 cm (5/7 vs 0/7; P =0.021).Conclusions 11 C-CHO PET/CT could improve the accuracy in T staging of NPC.It might also play a complementary role for 18 F-FDG PET/CT in the detection of HCC.