Purpose18F labelled PSMA-1007 presents promising results in detecting prostate cancer (PC), while some pitfalls exists meanwhile. An intra-individual comparison of 18F-FDG and 18F-PSMA-1007 in patients with prostate cancer were aimed to be performed in the present study. Then, the pitfalls of 18F-PSMA-1007 PET/CT in imaging of patients with prostate cancer were analyzed.Methods and Material21 prostate cancer patients underwent 18F-PSMA-1007 PET/CT as well as 18F-FDG PET/CT before treatment. All positive lesions were noticed in both 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT, then differentiated PC metastasis from benign lesions. the SUVmax, SUVmean and TBR of lesions, up to 10 metastases and 10 benign lesions per patients were recorded (5 for bone, 5 for soft tissue metastasis ). The distribution of positive lesions were analyzed for two imaging. Detection rates, SUVmax, SUVmean and TBR in 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT were compared, respectively. The optimal cut-off values of SUVmax, SUVmean for metastases vs. benign lesions was found through areas under ROC in 18F-PSMA-1007.ResultsThe detection rates of primary lesions in 18F-PSMA-1007 PET/CT was higher than that of 18F-FDG PET/CT(100% (21/21) vs. 67%(14/21)). For extra- prostatic lesions, 18F-PSMA-1007 PET/CT revealed 124 positive lesions, 49(49/124, 40%) attributed to a benign origin; 18F-FDG PET/CT revealed 68 positive lesions, 14(14/68, 21%) attributed to a benign origin. The SUVmax, SUVmean, TBR of primary tumor in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (15.20 vs. 4.20 for SUVmax; 8.70 vs. 2.80 for SUVmean; 24.92 vs. 4.82 for TBR, respectively); The SUVmax, SUVmean, TBR of metastases in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (10.72 vs. 4.42 for SUVmax; 6.67 vs. 2.59 for SUVmean; The TBR of metastases was 13.3 vs. 7.91). For 18F-FDG PET/CT, the SUVmax, SUVmean in metastases was higher than that in benign lesions (4.42 vs. 3.04 for SUVmax, 2.59 vs. 1.75 for SUVmean, respectively). Similarly, for 18F-PSMA-1007 PET/CT, the SUVmax, SUVmean in metastases was significantly higher than that in benign lesions(10.72 vs. 3.14 for SUVmax, 6.67 vs. 1.91 for SUVmean, respectively), ROC suggested that SUVmax=7.71, SUVmean=5.35 might be the optimal cut-off values for metastases vs. benign lesions.ConclusionThe pilot study suggested that 18F-PSMA-1007 showed superiority over 18F-FDG because its high detecting rate of PC lesions and excellent tumor uptake. While non-tumor uptake in 18F-PSMA-1007 may lead to misdiagnosis, recognizing these pitfalls and careful analysis can improve the accuracy of diagnosis.
Magnetic resonance contrast agents with T-T dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD-BSA nanoparticles (GGD-BSA NPs). The large size and porous structure endow GGD-BSA NPs with geometrical confinement, which restricts the tumbling of GGD and the diffusion of surrounding water molecules. As a result, GGD-BSA NPs exhibit ultrahigh T and T relaxivities, which are approximately 8-fold higher than those of gadolinium-based clinical contrast agents at 0.5 T. Besides, due to the intrinsic properties of their components, GGD-BSA NPs show good biocompatibility in vitro and in vivo, which warrants their great potential in clinical translation. Furthermore, GGD-BSA NPs show remarkable sensitivity in noninvasive detection of liver tumors by self-confirmed T-T dual-mode contrast-enhanced MRI. All of these merits make GGD-BSA NPs a potential candidate for fruitful biomedical and preclinical applications.
Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.
68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0–7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.
Dendritic cell (DC)-based vaccines have shown promising therapeutic results in cancer and some immune disorders. It is critical to track in vivo migration behaviours of DCs and monitor the whole process dynamically and non-invasively. Superparamagnetic iron oxide (SPIO) nanoparticles are chosen for DC labelling under magnetic resonance imaging (MRI) because of their proven biosafety as contrast agents. However, when used for cell labelling, sensitive biological indicators such as cell autophagy may be helpful to better understand the process and improve the probe design. Here, lactosylated N-Alkyl polyethylenimine coated SPIO nanoparticles are used for DC labelling. This probe shows satisfactory cell labelling efficiency and low cytotoxicity. In this study, autophagy was used as a key factor to understand how DCs react to nanoparticles after labelling. Our results demonstrate that the nanoparticles can induce protective autophagy in DCs, as inhibition of the autophagy flux could lead to cell death. Meanwhile, the nanoparticles induced autophagy could promote DC maturation which is an essential process for its migration and antigen presentation. Autophagy induced DC maturation is known to enhance the vaccine functions of DCs, therefore, our results suggest that beyond the MRI tracking ability, this probe might enhance therapeutic immune activation as well.
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