Wenhui Ma

Erratum to “Biodistribution and SPECT Imaging Study of 99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma”

In the paper titled “Biodistribution and SPECT imaging study of99mTc labeling NGR peptide in nude mice bearing human HepG2 hepatoma,” there is a mistake in the chemical structure of the NGR sequence and it is corrected in Figure 1 below. There is also a number mistake in the part of Materials and Methods (2.4. Cell Culture and Animal Model) that the HepG2 tumor model was established by subcutaneous injection of 5 × 106 HepG2 tumor cells (0.1 mL) into the right upper flanks, but not 2 × 106. Figure 1 Chemical structure and mass result of NGR (YGGCNGRC).

Cerenkov Luminescence Tomography of Aminopeptidase N (APN/CD13) Expression in Mice Bearing HT1080 Tumors

In vivo imaging of aminopeptidase N (APN/CD13) expression is crucial for the early detection of cancer. This study attempted to show that APN/CD13 expression can be imaged and quantified with novel Cerenkov luminescence tomography (CLT). Na131I with various activities was placed at different depths in a tissue-mimicking phantom, and various porcine tissues and luminescent images were acquired. The binding of 131I-NGR with human fibrosarcoma HT1080 and human colon cancer HT-29 cells was detected with Cerenkov luminescence imaging (CLI). Nude mice bearing HT-1080 tumors were imaged after injection with 131I-NGR using both planar and tomographic CLI methods. The penetration depth increased with ascending activity of Na131I. There was a robust linear correlation between the optical signal intensity and the HT1080 cell numbers (r2 = .9691), as well as the activity (r2 = .9860). The three-dimensional visualization CLT results clearly showed that 131I-NGR uptake in tumor tissues represented a high expression of the APN/CD13 receptor. CLT also allowed quantifying 131I-NGR uptake in tumor tissues showing an average activity of 0.1388 ± 4.6788E-6 MBq in tumor tissues. Our study indicated that 131I-NGR combined with CLT allowed us to image and quantify tumor-associated APN/CD13 expression noninvasively. The promising CLT technique could be potentially used for sensitively evaluating tumor angiogenesis in vivo.

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.

Propranolol Inhibits Glucose Metabolism and 18F-FDG Uptake of Breast Cancer Through Posttranscriptional Downregulation of Hexokinase-2

The advancement of breast cancer therapy is limited by the biologic behaviors of cancer cells, such as metastasis and recurrence. β-adrenoceptors (ADRB) are reported to be associated with the biologic behaviors of breast cancer and may influence glucose metabolism. Here, we sought to investigate the relationship between the activation of ADRB and the expression of glucose transporter (GLUT)-1 and hexokinase (HK)-2 and to clarify the impact of ADRB on 18F-FDG PET imaging in breast cancer. Methods: ADRB1/2 expression in 4T1, MDA-MB-231, and MCF-7 breast cancer cell lines was detected by Western blotting and immunofluorescence. ADRB-dependent regulation of GLUT-1 and HK-2 was determined by in vitro pharmacologic intervention. 4T1 breast cancer cells were treated with phosphate-buffered saline, isoproterenol, or propranolol, and the transcription and expression of GLUT-1 and HK-2 were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively. ADRB1/2 was, respectively, blocked by small-interfering RNA to investigate the direct relationship between ADRB1/2 and HK-2. To evaluate the impact of ADRB on 18F-FDG PET imaging, BALB/c mice bearing 4T1 tumors were injected with phosphate-buffered saline, isoproterenol, or propranolol, and 18F-FDG PET imaging was performed. The tumor-to-nontumor (T/NT) values of tumors and brown adipose tissue were calculated by defining the liver as a reference. The in vivo expression of GLUT-1 and HK-2 was observed by immunohistochemical analysis and Western blotting. Results: MDA-MB-231, MCF-7, and 4T1 breast cancer cells were positive for ADRB1/2 expression. The protein expression and posttranscriptional level of HK-2 were significantly decreased by treatment with propranolol in vitro, whereas GLUT-1 expression was not significantly altered by pharmacologic intervention. The expression of HK-2 could be reduced in ADRB2-blocked 4T1 cells. Mice in the propranolol-treated group exhibited lower T/NT values for the tumors and brown adipose tissue than the control group. Immunohistochemical analysis and Western blotting revealed reduced HK-2 expression in the tumors of propranolol-treated mice. Conclusion: The expression of HK-2 was regulated by the activation of ADRB2 in 4T1 breast cancer cells primarily at the posttranscriptional level. Additionally, propranolol prevented glucose metabolism and 18F-FDG PET imaging of 4T1 breast cancer tumors.

Biodistribution and SPECT Imaging Study of 99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

A peptide containing Asn-Gly-Arg(NGR) sequence was synthesized and directly labeled with 99mTc. Its radiochemical characteristics, biodistribution, and SPECT imaging were evaluated in nude mice bearing human HepG2 hepatoma. Nude mice bearing HepG2 were randomly divided into 5 groups with 5 mice in each group and injected with ~7.4 MBq 99mTc-NGR. The SPECT images were acquired in 1, 4, 8, and 12 h postinjection via caudal vein. The metabolism of tracers was determined in major organs at different time points, which demonstrated rapid, significant tumor uptake and slow tumor washout. The control group mice were blocked by coinjecting unlabelled NGR (20 mg/kg). Tumor uptake was (2.52 ± 0.83%) ID/g at 1 h, with the highest uptake of (3.26 ± 0.63%) ID/g at 8 h. In comparison, the uptake of the blocked control group was (1.65 ± 0.61%) ID/g at 1 h after injection. The SPECT static images and the tumor/muscle (T/NT) value were obtained. The highest T/NT value was 7.58 ± 1.92 at 8 h. The xenografted tumor became visible at 1 h and the clearest image of the tumor was observed at 8 h. In conclusion, 99mTc-NGR can be efficiently prepared and it exhibited good properties for the potential SPECT imaging agent of tumor.

64Cu-Labeled multifunctional dendrimers for targeted tumor PET imaging

We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with 64Cu for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5·NHAc dendrimers were then radiolabeled with 64Cu via the DOTA chelation. We show that the FA modification renders the dendrimers with targeting specificity to cancer cells overexpressing FR in vitro. Importantly, the radiolabeled 64Cu-DOTA-FA-FI-G5·NHAc dendrimers can be used as a nanoprobe for specific targeting of FR-overexpressing cancer cells in vitro and targeted microPET imaging of the FR-expressing xenografted tumor model in vivo. The developed 64Cu-labeled multifunctional dendrimeric nanoprobe may hold great promise to be used for targeted PET imaging of different types of FR-expressing 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.