Preclinical Evaluation of a Fibroblast Activation Protein and a Prostate-Specific Membrane Antigen Dual-Targeted Probe for Noninvasive Prostate Cancer Imaging.

Prostate-specific membrane antigen (PSMA) is a prostate cancer target that plays a crucial role in prostate cancer diagnosis and therapy. Herein, a novel dual-targeted imaging probe, [68Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 (68Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [68Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC50 values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC3 and A549, and significant differences in cell uptake were also observed. In vivo, [68Ga]Ga-FAPI-PSMA was rapidly cleared from the body, and the estimated radiation dose was relatively low compared with several other FAPI probes. In 22Rv1 and U87 MG tumor xenografts, [68Ga]Ga-FAPI-PSMA rapidly accumulated in tumors after administration, and the best images can be obtained at 1 h postinjection. In conclusion, the dual-targeted probe [68Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.

Higher accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

PURPOSE: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. METHODS: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. RESULTS: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. CONCLUSION: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

124I Radiolabeled Basiliximab for CD25-Targeted Immuno-PET Imaging of Activated T Cells.

Activated T cells played critical roles in immunotherapy and adoptive T cell therapy, and a non-invasive imaging strategy can provide us useful information concerning the transportation, accumulation, and homing of T cells in vivo. In this paper, by utilizing the long half-life radionuclide iodine-124 (124I) and CD25 specific monoclonal antibody Basiliximab, we have fabricated a novel probe, namely, 124I-Basiliximab, which was highly promising in the immuno-PET imaging of T cells. In vitro, 124I-Basiliximab had superior affinity to CD25 protein (Kd = 5.31 nM) and exhibited much higher accumulation in CD25 high-expression lymphoma cell line Karpas299 than that in CD25-negative cell line Daudi. In vivo, 124I-Basiliximab was excreted slowly from the body of mice, rendering it a relatively high effective dose (0.393 mSv/MBq) when applied in the immuno-PET imaging. In Karpas299 tumor xenograft, 124I-Basiliximab probe was observed to accumulate in the tumor quickly after tracer administration, with the optimal image acquired at 24 h post-injection. More importantly, PHA-activated hPBMC had much higher uptake of 124I-Basiliximab, indicating the potential utility of 124I-Basiliximab to discriminate activated hPBMC from its non-activated status. In summary, 124I-Basiliximab was fabricated for the first time, which can be applied in CD25-targeted immuno-PET imaging of activated T cells in vivo.

Clinical translational evaluation of Al18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging.

PURPOSE: In this study, a novel aluminium-[18F]fluoride (Al18F)-labelled 1,4,7­triazacyclononane-N,N',N″-triacetic acid (NOTA)-conjugated fibroblast activation protein inhibitor (FAPI) probe, named Al18F-NOTA-FAPI, was developed for fibroblast activation protein (FAP)-targeted tumour imaging; it could deliver hundreds of millicuries of radioactivity using automated synthesis. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated in both preclinical and clinical translational studies. METHODS: The radiolabelling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assays were completed with the U87MG and A549 cell lines to evaluate the affinity and specificity of the Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of the Al18F-NOTA-FAPI probe were researched in healthy Kunming (KM) and/or U87MG model mice. After the approval of the ethical committee, the Al18F-NOTA-FAPI probe was translated into the clinic for PET/CT imaging of the first 10 cancer patients. RESULTS: The radiolabelling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% using manual synthesis (n = 10), with a radiochemical purity over 99% and the specific activity of 9.3-55.5 MBq/nmol. The whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E - 02 mSv/MBq, which was lower than several other FAPI probes (68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour-bearing mice, Al18F-NOTA-FAPI showed good tumour detection efficacy based on the results of micro PET/CT imaging and biodistribution studies. In an organ biodistribution study of patients, Al18F-NOTA-FAPI showed a lower SUVmean than 2-[18F]-fluoro-2-deoxy-D-glucose (2-[18F]FDG) in most organs, especially in the liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI did not show extensive bone uptake, and was able to detect more lesions than 2-[18F]FDG in the PET/CT imaging of several patients. CONCLUSION: The Al18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein-targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour-bearing mice as well as in cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038080. Registered 09 September 2020. http://www.chictr.org.cn/showproj.aspx?proj=61192.

Near-Infrared Fluorescent Peptides with High Tumor Selectivity: Novel Probes for Image-Guided Surgical Resection of Orthotopic Glioma.

The complete excision of glioblastomas with maximal retention of surrounding normal tissues can have a positive effect on the survival status and quality of life of patients. Near-infrared fluorescence (NIRF) optical imaging of the tumor vasculature offers a noninvasive method for detection of early stage glioblastoma and efficient monitoring of therapeutic responses. The aim of this study was to develop a novel NIRF imaging probe as a visualization tool for image-guided surgical resection of orthotopic glioblastoma. In this study, Cy5.5-RKL, Cy5.5-NKL, and Cy5.5-DKL probes were successfully synthesized, and their properties were investigated in vitro and in vivo. In vivo, Cy5.5-RKL and Cy5.5-NKL were able to detect U87MG xenografts for at least 8 h post injection. The maximum tumor-to-muscle ratios of Cy5.5-RKL and Cy5.5-NKL were 7.65 ± 0.72 and 5.43 ± 0.72, respectively. Of the probes, Cy5.5-RKL displayed the best delineation of the boundaries between orthotopic glioblastomas and normal brain tissue at 8 h p.i. In conclusion, NIRF imaging using Cy5.5-RKL is promising not only for diagnostic purposes but also for use in image-guided surgery for orthotopic glioblastoma or other superficial tumors.

A ratiometric upconversion nanoprobe for fluorometric turn-on detection of sulfite and bisulfite.

A nanoprobe is described for the ratiometric fluorometric determination of sulfite ions. Upconversion nanoparticles (UCNPs) of the type ß-NaYF4:Yb(III),Er(III),Tm(III) were covalently modified with the molecular probe HIAN which is a hydroxynaphthalimide fluorophore modified with a (cationic) indolinium moiety. Under excitation at 980 nm, the green emission of the UCNPs (peaking at 543 nm) is almost totally quenched, while the NIR emission (peaking at 802 nm) remains unaffected. In the presence of sulfite or bisulfite (hydrogen sulfite), the green fluorescence is restored and can be visually observed. A ratiometric method was worked out by measurement of the ratio of the green and NIR emissions. The analytical range extends from 10 to 250 µM, the limit of detection is 0.14 µM, and the assay can be performed within 40 s. Graphical abstract Based on the use of a molecular probe for sulfite and hydrogen sulfite, and by exploiting an inner filter effect (IFE), an assay for sulfite/hydrogen sulfite was developed by using upconversion nanoparticles (UCNPs). Addition reaction of sulfite/bisulfite with the material results in weakened IFE and enhanced green fluorescence of the UCNPs at excitation/emission wavelengths of 980/543 nm.

Fibroblast Activation Protein and Glycolysis in Lymphoma Diagnosis: Comparison of 68Ga-FAPI PET/CT and 18F-FDG PET/CT.

Our objective was to compare the diagnostic performance of 68Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and 18F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. Methods: Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent 68Ga-FAPI and 18F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples t test and Wilcoxon signed-rank test were used to compare parameters. The correlation between the immunochemistry results and tracer uptake was determined by the Spearman rank correlation coefficient. Results: In total, 186 participants (median age, 52 y [interquartile range, 41-64 y]; 95 women) were included. Dual-tracer imaging produced 3 types of imaging profiles. 18F-FDG PET possessed a higher staging accuracy (98.4%) than 68Ga-FAPI PET (86.0%). In 5,980 lymphoma lesions, 18F-FDG PET/CT detected more nodal (4,624 vs. 2,196) and extranodal (1,304 vs. 845) lesions than 68Ga-FAPI PET/CT. Additionally, 52 68Ga-FAPI-positive/18F-FDG-negative lesions and 2,939 68Ga-FAPI-negative/18F-FDG-positive lesions were observed. In many lymphoma subtypes, semiquantitative evaluation revealed no significant differences in SUVmax or target-to-liver ratios between 68Ga-FAPI and 18F-FDG PET/CT (P > 0.05). Interestingly, GLUT1 and hexokinase 2 were overexpressed both in lymphoma cells and in the tumor microenvironment, whereas FAP was expressed only in stromal cells. FAP and GLUT1 expression correlated positively with 68Ga-FAPI SUVmax (r = 0.622, P = 0.001) and 18F-FDG SUVmax (r = 0.835, P < 0.001), respectively. Conclusion: 68Ga-FAPI PET/CT was inferior to 18F-FDG PET/CT in diagnosing lymphomas with low FAP expression. However, the former may supplement the latter and help reveal the molecular profile of lymphomas.

Characterizing Concomitant Follicular Lymphoma and Gastric Carcinoma Using 68Ga-FAPI-04 and 18F-FDG PET/CT.

ABSTRACT: We herein report a case involving a 67-year-old man with concomitant progressive follicular lymphoma and gastric carcinoma. Baseline 18F-FDG PET/CT showed high metabolic activity in multiple nodal stations and a thickened gastric antrum wall, whereas 68Ga-FAPI-04 PET/CT depicted very intense tracer uptake in the gastric lesion but mild uptake in the nodes. After the treatment, complete remission from lymphadenopathy was achieved, whereas the gastric lesion accumulated more radiotracers compared with baseline levels. Despite our incorrect initial assumption of B-cell transformation, molecular imaging was able to profile the characteristics of these 2 diseases.

The 68 Ga-DOTA-FAPI-04 PET/CT for the differential diagnosis of solitary fibroma of pleura from other chest disease with low uptake of 18 F-FDG.

OBJECTIVE: We conducted a prospective study using 68 Ga-DOTA-FAPI-04 PET/computed tomography (CT) to differentiate solitary fibromas of pleura (SFP) from other chest similar masses showing low uptake of 18 F-FDG. METHODS: A prospective study including 13 patients was divided into two groups: five cases of SFP and eight of thoracic lesions resembling SFP on general imaging examination. Except for CT and MRI, all patients underwent both 18 F-FDG and 68 Ga-DOTA-FAPI-04 PET/CT examinations. Compare the differences of lesions in CT net enhancement value and the uptake of 18 F-FDG and 68 Ga-DOTA-FAPI-04 between the two groups. The values of CT and PET/CT for differential diagnosis were calculated by receiver operating characteristic (ROC) curves. RESULTS: The uptake of 68 Ga-DOTA-FAPI-04 in SFP was significantly higher than the others in chest, SUVmean (8.10 ± 5.57) versus (1.11 ± 0.38); and SUVmax (15.46 ± 8.16) versus (3.96 ± 2.43), and the difference was statistically significant ( P < 0.05). The 68 Ga-DOTA-FAPI-04 could effectively distinguish SFP from other lesions, and the accuracies of SUVmax and SUVmean for differential diagnosis were 92.31 and 100%, the corresponding cutoff value being 7.19 and 2.26. The uptake of 18 F-FDG in SFP was slightly lower than other lesions, SUVmean (1.63 ± 0.30) versus (1.88 ± 1.02); and SUVmax (2.51 ± 0.54) versus (3.60 ± 1.57), and the difference was not statistically significant ( P > 0.05). The SFP showed significant enhancement in the venous phase, but the difference was not statistically significant ( P > 0.05). CONCLUSION: The 68 Ga-DOTA-FAPI-04 has potential application value in differentiating SFP from lesions with low 18 F-FDG uptake, in addition, 68 Ga-DOTA-FAPI-04 may specifically target SFP.

Diagnostic value of [68Ga]Ga-FAPI-04 in patients with colorectal cancer in comparison with [18F]F-FDG PET/CT.

Purpose: This study aimed to compare the diagnostic performance of [68Ga]Ga-FAPI-04 PET/CT and [18F]F-FDG PET/CT in primary and metastatic colorectal cancer (CRC) lesions. Methods: This single-center preliminary clinical study (NCT04750772) was conducted at the Peking University Cancer Hospital & Institute and included 61 participants with CRC who underwent sequential evaluation through PET/CT with [18F]F-FDG and [68Ga]Ga-FAPI-04. Their PET/CT images were analysed to quantify the uptake of the two tracers in the form of maximum standardised uptake (SUVmax) values and target-to-background ratio (TBR), which were then compared using Wilcoxon's signed-rank test. The final changes in the tumour-node-metastasis (TNM) stage of all participants were recorded. Results: Of all the participants, 21 were treatment naïve and 40 had been previously treated. In primary CRC lesions, the average TBRs of [68Ga]Ga-FAPI-04 and [18F]F-FDG were 13.3 ± 8.9 and 8.2 ± 6.5, respectively. The SUVmax of [68Ga]Ga-FAPI-04 in signet-ring/mucinous carcinomas (11.4 ± 4.9) was higher than that of [18F]F-FDG (7.9 ± 3.6) (P = 0.03). Both median SUVmax in peritoneal metastases and TBR in liver metastases of [68Ga]Ga-FAPI-04 were higher than those of [18F]F-FDG (5.2 vs. 3.8, P < 0.001; 3.7 vs. 1.9, P < 0.001, respectively). Compared with [18F]F-FDG PET/CT, clinical TNM staging based on [68Ga]Ga-FAPI-04 PET/CT led to upstaging and downstaging in 10 (16.4%) and 5 participants (8.2%), respectively. Therefore, the treatment options were changed in 13 participants (21.3%), including 9 with additional chemo/radiotherapy and/or surgery and others with avoidance or narrowed scope of surgery. Conclusion: [68Ga]Ga-FAPI-04 showed potential as a novel PET/CT tracer to detect lymph nodes and distant metastases, which improved CRC staging, thus prompting the optimisation or adjustment of treatment decisions.

Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT.

Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of 68Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent 68Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the 68Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate 68Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate 68Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUVmax (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion:68Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.

Dynamic PET/CT Imaging of 68Ga-FAPI-04 in Chinese Subjects.

This study aims to further explore dynamic 68Ga-FAPI-04 PET/CT imaging of healthy Chinese subjects and lung cancer patients. Moreover, the variability of 68Ga-FAPI-04 uptake in normal organs was measured to provide a basis for analyzing its biological distribution, interpreting auxiliary images, determining the reliability of image quantification, and monitoring treatment. Six patients (3 subjects without tumors and 3 lung cancer patients) separately underwent 68Ga-FAPI-04 and 2-[18F]FDG PET/CT imaging within 1 week. The biodistribution and internal radiation dosimetry were reported and compared with data previously obtained from Caucasian patients. Moreover, the mean SUV (standardized uptake value) was normalized to body mass or to lean body mass (SUL), and the coefficients of variation (CVs) were calculated and compared for each volume of interest. The average whole-body effective dose was calculated to be 1.27E-02 mSv/MBq, which was comparable with previously reported results of 68Ga-FAPI-04 probes. Furthermore, the SUVmean was slightly higher than the SULmean in most organs; however, the CV of the SULmean for most organs was higher than that of the SUVmean at later time points. In the liver, the CV of the SUVmean was lower (12.7%) than that of the SULmean and was similar to the CV for corresponding 2-[18F]FDG PET/CT value (11.8%). In addition, 68Ga-FAPI-04 PET/CT showed good efficacy for diagnosing lung cancer patients in this study. A comparison of the radiation dosimetry obtained before from a Caucasian population demonstrated no clinically significant differences between these two populations after 68Ga-FAPI-04 injection. The variability in most organs was slightly lower for SUVmean than for SULmean, suggesting that SUVmean may be the preferable parameter for quantifying images obtained with 68Ga-FAPI-04. In addition, 68Ga-FAPI-04 PET/CT imaging is expected to be a promising tool for diagnosing lung cancer.

PET/CT using 68 Ga-PSMA-617 versus 18 F-fluorodeoxyglucose to differentiate low- and high-grade gliomas.

BACKGROUND AND PURPOSE: To compare and characterize metabolic features of high- and low-grade glioma tumors using 68 Ga-PSMA-617 and 18 F-FDG positron emission tomography/computed tomography (PET/CT). METHODS: Thirty patients who underwent both 68 Ga-PSMA-617 and 18 F-FDG PET/CT over 2 consecutive days and then underwent surgical treatment were retrospectively identified. All tumors were diagnosed histologically. This report includes 16 high-grade glioma (HGG) and 14 low-grade glioma (LGG) tumors. Standard uptake value (SUV) and target to nontarget (T/NT) were quantitatively investigated through the entire tumor region. Statistical analyses were performed using area under the curve (AUC) and comparison of two means. RESULTS: SUVmax and SUVmean were the most effective (AUC, 0.96 and 0.94 for PSMA PET; AUC, 0.79 and 0.74 for FDG PET, respectively) for differentiating HGGs from LGGs. These methods distinguished between HGG and LGG effectively (PSMA PET: SUVmax , 5.766 ± 3.945 vs. 0.7364 ± 0.5295, p < 0.0001; SUVmean , 1.666 ± 1.680 and 0.1514 ± 0.1534, p < 0.0001, respectively) (FDG PET: SUVmax , 11.67 ± 3.639 and 9.118 ± 6.612; SUVmean , 5.648 ± 2.114 and 4.435 ± 2.872; p = 0.0083, 0.0262, respectively). The Youden index for SUVmax and SUVmean of 68 Ga-PSMA-617 and 18 F-FDG were 0.82 and 0.79 and 0.54 and 0.61, separately. T/NTmax was helpful for visual inspection of 68 Ga-PSMA-617-PET images (T/NTmax : 1.291 ± 0.9553 in grade II, 5.25 ± 2.435 in grade III, and 13.61 ± 13.84 in grade IV). T/NTmax differed significantly between LGG and HGG and between subtypes of LGG. CONCLUSION: PET/CT with 68 Ga-PSMA-617 and 18 F-FDG may help distinguish between HGG and LGG, and 68 Ga-PSMA-617 PET/CT is superior to18 F-FDG in differentiating HGG and LGG.

Biodistribution, Radiation Dosimetry, and Clinical Application of a Melanin-Targeted PET Probe, 18F-P3BZA, in Patients.

N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA) is a radiotracer that demonstrates high binding selectivity and affinity in melanoma. The aim of the present study was to estimate the biodistribution and clinical radiation dosimetry of 18F-P3BZA in healthy volunteers and perform a preliminary clinical application for PET/CT imaging in melanoma patients. Methods:18F-P3BZA was produced efficiently with a radiosynthesizer. Six healthy volunteers were injected with 18F-P3BZA (211.7 ± 15.4 MBq) followed by serial whole-body PET/CT scans and blood tests to assess biodistribution, pharmacokinetic, and radiation dosimetry at 10 min, 1 h, 2 h, and 4 h after injection. The vital signs of volunteers were recorded in regular intervals during the imaging sessions. The effective dose for each subject after the medical internal radiation dosimetry schema was calculated with OLINDA/EXM software. For the preliminary clinical application, 5 patients with suspected melanomas underwent 18F-P3BZA PET/CT imaging at 10 min and 1 h after injection. All patients also underwent 18F-FDG PET/CT scans on the third day to compare the potential diagnostic ability of 18F-P3BZA with 18F-FDG. Results: The radiochemistry yield of 18F-P3BZA labeling was 12.3% ± 3.9%, and the purity of 18F-P3BZA after purification and formulation was higher than 99.5%. The highest uptake of 18F-P3BZA was in the liver with an SUVmean of 8.3 ± 1.0 at 10 min after injection. The resultant whole-body effective dose was 0.0193 mSv/MBq. 18F-P3BZA showed high uptake and suggested an ability for specific imaging of melanoma and its metastasis in patients. The average SUVmean of 18F-P3BZA and 18F-FDG in tumors was 19.7 ± 5.3 and 10.8 ± 2.7 at 60 min after injection. Conclusion: Our study suggests that 18F-P3BZA is safe and compatible for clinical use. The first-in-human clinical application to melanoma showed favorable delineated tumors in patients, demonstrating the potential of 18F-P3BZA for diagnostic PET imaging of melanoma.

Brain mGluR5 in Shank3B-/- Mice Studied With in vivo [18F]FPEB PET Imaging and ex vivo Immunoblotting.

Although several studies have found that metabotropic glutamate 5 receptor (mGluR5) may play an important role in autism spectrum disorders (ASD), the mechanisms remain unclear. Here, we used a Shank3 gene complete knockout mouse model (Shank3B-/-) to explore the change in mGluR5 in the brain. To assess whether deletion of Shank3 in mice results in ASD-like behavior, we conducted a battery of behavioral experiments to characterize Shank3B-/- mice, including repetitive grooming behavior tests, three-chamber tests and resident-intruder tests. Wild-type C57/BL6 and Shank3B-/- mice underwent PET scans with [18F]FPEB, which was highly specific to mGluR5. Mouse brains were extracted post-scan, and mGluR5 protein levels were assessed by immunoblotting. The binding potential (BPnd) of mGluR5 was rich in the hippocampus, thalamus, striatum, and amygdala. More importantly, Shank3B-/- mice showed significantly increased BPnd compared to the control mice in these brain regions. Immunoblotting revealed elevated mGluR5 levels in the hippocampus, thalamus, and amygdala but not in the striatum compared with control mice. These findings indicated that [18F]FPEB could visualize mGluR5 in the mouse brain. The deficiency of Shank3 can impair mGluR5 expression in multiple brain regions. Future work is also needed to understand the reasons for different results between in vivo PET and ex vivo immunoblotting.

Upconversion nanocomposites for photo-based cancer theranostics.

Lanthanide ion doped upconversion nanoparticles (UCNPs) are known to be able to convert long-wavelength excitation light (usually 980 nm) into high-energy ultraviolet (UV) or visible emissions, and they have attracted significant attention because of their distinct photochemical properties including sharp emission bands, low autofluorescence, high tissue penetration depth, inertness to ambient interference and minimal photodamage to tissues. Until now, UCNPs have shown great potential in various realms including bioimaging, biosensing and biomedical applications. Especially in recent years, UCNP based nanocomposites have been found to be promising tools for multi-modal imaging and low-invasive photo-based therapy of tumors. In this review, we summarize the recent achievement and progress of UCNP based multifunctional nanoplatforms for bioimaging and cancer phototheranostics, including photodynamic therapy (PDT) and photothermal therapy (PTT). Furthermore, some emerging trends, future directions as well as challenges in this rapidly growing field are discussed.

Chemistry and biology of glycopeptides with antibiotic activity.

Glycopeptides with potent antibiotic activity are vital for the treatment of severe infections that caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. Recently, the glycopeptide-resistant Grampositive bacteria present a serious challenge to public health after more than decades of clinical use. Additionally, the antibacterial activity and side effect become an increasing crisis and should have to be taken into account. As a consequence, new glycopeptide antibiotics are needed to face with these problems. In the past years, with the development of natural product chemistry, more and more glycopeptide compounds with promising biological properties were discovered. In addition, the chemical modification of the known glycopeptide provides an opportunity for the discovery of new potential glycopeptide antibiotics. Considerable efforts have been made in this field in order to meet the clinical needs. In this article, we mainly focus on the advances of glycopeptide as antibiotics, including many representative glycopeptides or its analogues and derivatives. Taken together, we hope all this information is helpful for the discovery of new potential glycopeptide antibiotics.

Determination and pharmacokinetic study of the novel anti-tumor candidate drug DG-7 in rat plasma by liquid chromatography-tandem mass spectrometry.

DG-7 (11,14-dihydroxy-7,20-epoxy-20-O-derivative of ent-kaurene diterpenoid) is a novel anti-tumor candidate drug. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DG-7 in rat plasma. An aliquot of 50 µL plasma sample was prepared by liquid-liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Waters XTerra C18 column (2.1 mm × 150 mm, 5 µm) with an isocratic elution system consisting of methanol and water. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transitions for MRM were m/z 590.1→m/z 260.0 for DG-7 and m/z 180.3→m/z 110.1 for phenacetin (internal standard). The method was linear over the concentration range of 5-2,500 ng/mL. The intra- and inter-day precisions were less than 7.9% and the accuracy was within ± 9.0%. The mean recovery of DG-7 ranged from 76.8% to 79.2%. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of DG-7.