Shengjun Wang

The Prognostic Value of 18F-FDG PET/CT for Hepatocellular Carcinoma Treated with Transarterial Chemoembolization (TACE)

18F-Fluoro-deoxyglucose (FDG) PET/CT can be used to monitor the biological behavior of hepatocellular carcinoma (HCC). Baseline PET/CT has prognostic value in HCC patients, but there is litter knowledge of the PET/CT changes after treatment. We evaluated 27 HCC patients treated with transarterial chemoembolization (TACE) from June 2011 to July 2012, and we investigated the prognostic value of PET/CT. Patients were followed up with regular clinical and laboratory examinations and contrast-enhanced spiral computed tomography (CT). Furthermore, PET/CT assessments were collected and analyzed before (range 1~15 d) and after the first month of TACE (range, 27~45d). We tested the prognostic value of the tumor standardized uptake value (TSUV) and normal liver SUV(LSUV) according to the VOI (volume of interest). The SUVs were used to assess the relationship between the treatment response and survival. To assess their prognostic value, we evaluated the areas under the receiver operating characteristic (ROC) curves of different SUVs for predicting survival. Finally, the median overall survival (OS) and time to progression (TTP) for 27 patients were 15.4 months (95%CI, 3.3-27.5 months) and 11.4 months (95%CI, 6.7-16.1 months), respectively. The ΔTSUVmax%, based on the VOI, had the highest discriminative prognostic value and the cutoff PET/CT response was 0.1 with a sensitivity of 100% and a specificity of 95.2%. The OS was significantly better in the PET/CT response group than in the PET/CT non-response group (p=0.025). In conclusion, an early interim PET/CT after TACE may have prognostic value for HCC patients treated with TACE, and the ΔTSUVmax% may help in determining the HCCs viability in patients with high baseline and follow-up18F-FDG uptake.

Prospective Study of 68 Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients

Purpose: The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, 68Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients. Methods: Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after 68Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both 68Ga-NOTA-NFB and 18F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining. Results: 68Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of 68Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of 18F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent 68Ga-NOTA-NFB uptake. Conclusion: With a favorable radiation dosimetry profile, 68Ga-NOTA-NFB is safe for clinical imaging. Compared to 18F-FDG PET/CT, 68Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.

Comparing the Diagnostic Potential of 68Ga-Alfatide II and 18F-FDG in Differentiating Between Non–Small Cell Lung Cancer and Tuberculosis

The objectives of this study were to compare the diagnostic potential of 68Ga-Alfatide II with18F-FDG in differentiating between non–small cell lung cancer patients (NSCLC) and lung tuberculosis (TB) patients. Methods: Twenty-one NSCLC patients and 13 TB patients were recruited. PET/CT images using either 68Ga-Alfatide II or 18F-FDG were acquired in 2 consecutive days. SUV quantitative comparison, receiver-operating curve analysis, and comprehensive visual analysis were performed. The expression of the angiogenesis marker αvβ3 in NSCLC and TB primary lesions was analyzed by immunohistochemistry. Results: The 68Ga-Alfatide II SUVmax and SUVmean were significantly different in NSCLC and TB (P = 0.0001 and 0.0007, respectively). The area under the receiver-operating curve value of 68Ga-Alfatide II SUVmax was significantly higher than that of 18F-FDG (P = 0.038). The visual differentiation diagnostic specificity of 68Ga-Alfatide II was 1.57-fold (84.62% vs. 53.85%) higher than that of 18F-FDG. In the detection of NSCLC lymph nodes, 68Ga-Alfatide II was superior in specificity (100% vs. 66.7%), whereas the sensitivity was greater with 18F-FDG (87.5% vs. 75%). In TB lymph node detection, the false-positive rate of 68Ga-Alfatide II was one-third (15.4%/46.2%) the value of 18F-FDG. Additionally, 68Ga-Alfatide II detected more metastases in the brain but less in the liver and the bone. The αvβ3 biomarker was specifically expressed in the cells and the neovasculature of NSCLC lesions. Conclusion: 68Ga-Alfatide II is qualified for detecting NSCLC primary lesions and is superior to 18F-FDG in distinguishing NSCLC from TB in primary lesions and suggestive lymph nodes. 68Ga-Alfatide II is more likely to be capable of detecting brain metastasis, and 18F-FDG is more likely to be capable of detecting liver and early-stage bone metastases.

Evaluation of 68Ga-labeled iNGR peptide with tumor penetrating motif for microPET imaging of CD13-positive tumor xenografts

The aim of the study is to evaluate the efficacy of 68Ga-labeled iNGR, containing Asn-Gly-Arg (NGR) homing sequence and CendR (R/KXXR/K) penetrating motif, as a new molecular probe for microPET imaging of CD13-positive xenografts. The synthesized iNGR and NGR peptides were conjugated with DOTA and then labeled with 68Ga. 68Ga-iNGR and 68Ga-NGR were compared in the performance of the in vitro stability, partition coefficient, binding affinity, cell uptake analysis, in vivo microPET imaging, and biodistribution studies in CD13-positive HT-1080 and CD13-negative HT-29 cell lines. The in vitro results revealed that both probes exhibited high radiochemical purity and stability, and no significant difference between two probes was observed in terms of the binding affinity to CD13. In vivo microPET/CT imaging showed that the uptake of 68Ga-iNGR in HT-1080 tumor was significantly higher than that of 68Ga−NGR. Moreover, tumor 68Ga-iNGR uptake could be completely blocked by cold NGR and partially blocked by neutralizing NRP-1 antibody. We concluded that 68Ga-iNGR has a higher tumor uptake and better tumor retention than 68Ga-NGR through NRP-1, indicating that CendR motif modification is a promising method for improving NGR peptide performance.

Reduction in the recurrence of meningiomas by combining somatostatin receptor scintigraphy of 99mTc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held γ-probe during surgery

PurposeThe aim of this study was to determine whether recurrence of meningiomas could be reduced by combining somatostatin receptor scintigraphy (SRS) of 99mTc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held &ggr;-probe during surgery. Materials and methodsThirty patients with meningiomas diagnosed by MRI and considered as the study group were treated with 99mTc-HYNIC-octreotide SPECT/CT preoperatively and pathologically examined postoperatively. Another 60 patients considered as the control group underwent only an MRI preoperatively and a pathological examination postoperatively. For the patients in the study group, meningiomas were removed by a hand-held &ggr;-probe 4–12 h after SRS; these patients were followed up by MRI examination each year for 5 years to monitor the recurrence rate of the meningiomas. For the control group, routine operations without radio guidance were performed and followed up with MRI examination simultaneously. ResultsAll patients in the study group, comprising 20 with grade I and 10 with grade II meningiomas, showed high 99mTc-HYNIC-octreotide accumulation with a sensitivity of 100% for SRS; four patients (13.3%) relapsed after a 5-year follow-up, including one (5%) patient with a grade I and three (30%) patients with a grade II meningioma. However, among the 60 control patients, 30 were of grade I and 30 were of grade II; 18 patients (30%) experienced recurrence, including five (16.7%) grade I patients and 13 (43.3%) grade II patients. There were significant differences in recurrence between the study group and the control group when considering all the patients and those in grade I and grade II (all P values were below 0.001). Conclusion 99mTc-HYNIC-octreotide SPECT/CT SRS is a sensitive technique for detecting meningiomas, and radio guidance using a hand-held &ggr;-probe with 99mTc-HYNIC-octreotide during surgery can significantly reduce the recurrence of meningiomas.

Inter-heterogeneity and intra-heterogeneity of αvβ3 in non-small cell lung cancer and small cell lung cancer patients as revealed by 68Ga-RGD2 PET imaging

PurposeIntegrin αvβ3 is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare αvβ3 levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer 68Ga-labeled dimerized-RGD (68Ga-RGD2).MethodsThirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using 68Ga-RGD2.18F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker αvβ3 in NSCLC and SCLC lesions was analyzed by immunohistochemistry.ResultsThe 18F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The 68Ga-RGD2 uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of 68Ga-RGD2 SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that αvβ3 integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression.ConclusionsThe uptake of 68Ga-RGD2 in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower αvβ3 target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of αvβ3 also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of αvβ3 may potentially improve current applications of αvβ3-targeted therapy and diagnostic imaging in lung cancer.

Was [18F]Fluorodeoxyglucose Positron Emission Tomography Complete Response After Chemoradiotherapy Defined As Standardized Uptake Valuemax-1 hour ≤ 3 Complete?

TO THE EDITOR: In the article by Monjazeb et al, the authors defined [F]fluorodeoxyglucose (FDG) –positron emission tomography (PET) complete response (CR) after chemoradiotherapy (CRT) as standardized uptake value (SUV)max-1 hour 3. We think that this description is not exact or sufficient. It may have only a moderate correlation with individual estimates, partially explaining cell differentiation and the response to CRT. Patients in the low SUV group were less likely to show evidence of treatment response after CRT, including a higher likelihood of residual nodal disease and a lower likelihood of a pathologic CR and estimated treatment response. Adding SUV (initial-to-post CRT scan ratio) combined with histologic differentiation to give the conclusion suggesting a certain pharmacodynamic invariance of reference tissue index. The authors provided no information on the interval between the first PET scan and CRT. A prolonged delay between PET-CR and CRT may defer the diagnostic value of PET-CR and may result from coexisting conditions that would themselves have a negative effect on survival. Jingu et al gave more reasonable selection criteria—such as no previous radiation therapy, FDG-PET performed less than 2 weeks before CRT, no serious diabetes, along with other criteria. Hurmuzlu et al found alcohol abuse and number of positive lymph nodes to be prognostic factors for overall survival. During the follow-up, did the patients get any therapy that would affect the outcomes? The time and number of cycles of CRT are also important. Abate et al reported that 2% to 3% of recurrences were detected each year, which suggests that annual follow-up is adequate. Survival after recurrence was improved with therapy and confirms the use of careful follow-up in these patients. Moreover, more information about incomplete resections should be given, and different surgery intentions should be considered. It should be noted that, in the trial by Chao et al, aggressive surgical treatment after CRT was reserved for patients for whom complete resection was anticipated. In addition, FDG-PET images were interpreted by an experienced nuclear radiologist and correlated with computed tomography, but more than two specialists working side by side in consensus to evaluate the PET images would be better. Neither reader should be aware of patients’ clinical or follow-up data.