Longitudinal 18F-VUIIS1008 PET imaging in a rat model of rheumatoid arthritis.

Macrophages have crucial roles in the pathogenesis of rheumatoid arthritis (RA). We aimed to elucidate the temporal profile of macrophage infiltration in synovitis in RA rat models using PET (positron emission tomography) imaging based a new generation of TSPO (Translocator protein, 18 kDa)-PET ligand, 18F-VUIIS1008 {2-[5,7-Diethyl-2-{4-[2-(18F)fluoroethoxy]phenyl}pyrazolo(1,5-a)pyri-midin-3-yl]-N, N-diethylacetamide}. In vitro and in vivo studies were conducted using RAW264.7 macrophage cells and a rat model of RA induced by Complete Freund's Adjuvant (CFA). Our results showed 18F-VUIIS1008 showed excellent stability in vitro and binding specificity to RAW264.7 cells, and rapid accumulation in the left inflammatory ankles. PET studies revealed that 18F-VUIIS1008 could clearly identify the left inflammatory ankles with good contrast at 30-120 min post-injection. The uptake of 18F-VUIIS1008 of left inflammatory ankles was a wiggle trace with two peaks on day 7 and 29, and then, the highest peak uptake was seen on day 29 (3.00% ± 0.08%ID/g) at 60 min after injection. Tracer uptakes could be inhibited by PK11195 or VUIIS1008. Immunohistochemistry and immunofluorescence tests showed that elevated TSPO expression and infiltrated macrophages were found in the left inflammation ankles. 18F-VUIIS1008 as a novel PET imaging agent showed great potential to identify temporal profile of macrophage infiltration in synovitis in RA, and deliver accurate non-invasive diagnosis and real-time monitoring of RA development.

Preclinical Evaluation of a Novel 99mTc-Labeled CB86 for Rheumatoid Arthritis Imaging.

Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m (99mTc)-labeled TSPO ligand (99mTc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-a]-pyridin-3-yl]-N,N-di-n-propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro; however, few 99mTc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 (ca. 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare 99mTc-labeled CB86, and its evaluation as a 99mTc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of 99mTc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of 99mTc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and 99mTc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of 99mTc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of 99mTc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, 99mTc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, 99mTc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. 99mTc-SPECT imaging studies revealed that 99mTc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30-180 min after injection. Therefore, 99mTc-DTPA-CB86 may be a promising probe for arthritis 99mTc-SPECT imaging.

Organelle-Partitioned Sugar-Rhodamine Diad for In Vivo Tumor Imaging.

Current tumor imaging agents are often limited by their liability to dissipate from tumor tissues. As cell sugar sorting enables exogenous sugars to be delivered into predetermined subcellular locations, we synthesized sialic acid (Sia) derivatives with rhodamine-X conjugated at C-9 (ROXSia), which hitchhikes cell sialic acid sorting to target tumor cell lysosomes, exhibiting pH-independent long-term probe retention in lysosomes. ROXSia gives selective, bright, and endured fluorescence signals in subcutaneous tumors and orthotopic tumors in mice models. These results indicate the potential of ROXSia as a lysosome-targeted optical agent for fluorescence-guided tumor resection.

Optimal Saturated Neuropilin-1 Expression in Normal Tissue Maximizes Tumor Exposure to Anti-Neuropilin-1 Monoclonal Antibody.

BACKGROUND: As involved in tumor angiogenesis, Neuropilin Receptor type-1 (NRP-1) serves as an attractive target for cancer molecular imaging and therapy. Widespread expression of NRP-1 in normal tissues may affect anti-NRP-1 antibody tumor uptake. OBJECTIVE: To assess a novel anti-NRP-1 monoclonal antibody A6-11-26 biodistribution in NRP-1 positive tumor xenograft models to understand the relationships between dose, normal tissue uptake and tumor uptake. METHODS: The A6-11-26 was radiolabeled with 131I and the mice bearing U87MG xenografts were then administered with 131I-labelled A6-11-26 along with 0, 2.5, 5, and 10mg·kg-1 unlabelled antibody A6-11-26. Biodistribution and SPECT/CT imaging were evaluated. RESULTS: 131I-A6-11-26 was synthesized successfully by hybridoma within 60min. It showed that most of 131IA6- 11-26 were in the plasma and serum (98.5 ± 0.16 and 88.9 ± 5.84, respectively), whereas, less in blood cells. For in vivo biodistribution studies, after only injection of 131I-A6-11-26, high levels of radioactivity were observed in the liver, moderate level in lungs. However, liver and lungs radioactivity uptakes could be competitively blocked by an increasing amount of unlabeled antibody A6-11-26, which can increase tumor radioactivity levels, but not in a dose-dependent manner. A dose between 10 and 20mg·kg-1 of unlabeled antibody A6-11-26 may be the optimal dose that maximized tumor exposure. CONCLUSION: Widespread expression of NRP-1 in normal tissue may affect the distribution of A6-11-26 to tumor tissue. An appropriate antibody A6-11-26 dose would be required to saturate normal tissue antigenic sinks to achieve acceptable tumor exposure.

Plain and contrast-enhanced chest computed tomography scan findings of pulmonary cryptococcosis in immunocompetent patients.

Pulmonary cryptococcosis is most commonly reported in immunocompromised patients, whereas immunocompetent hosts are rarely affected and may be asymptomatic, resulting in reduced diagnostic performance of computed tomography (CT) imaging. Thus, the aim of the present study was to review the plain and contrast-enhanced chest CT scan findings of primary pulmonary cryptococcosis in immunocompetent patients, with the aim of improving the diagnosis of this type of pulmonary disease. In the present study, a total of 27 immunocompetent patients of clinically confirmed pulmonary cryptococcosis were analyzed retrospectively. Of the 27 patients, 14 patients underwent plain and contrast-enhanced chest CT scans, while 13 patients only underwent plain chest CT scanning. The clinical and imaging characteristics, including the location, shape, size, number, edge and attenuation or intensity of each lesion, in unenhanced and contrast-enhanced CT scans were reviewed. The results indicated that the most common CT finding was pulmonary nodules (40.74%), with multiple nodules (25.93%) being more common compared with solitary nodules (14.81%). The majority of the nodules were poorly defined and inhomogeneous with observed air-bubble sign. Other findings included consolidation (25.93%), ground-glass opacities (GGO; 22.22%) and a mass (11.11%). The halo, air bronchogram and cavity signs were observed more frequently (22.22, 18.52 and 14.81%, respectively). The pulmonary lesions presented a predominant distribution in the lower lung lobes and peripheral area in 55.55 and 74.07% of the cases, respectively. On the contrast-enhanced CT images, the majority of nodules presented ring enhancement with the mean maximal enhancement value of 20.92±5.67 Hu, and masses demonstrated inhomogeneous enhancement with a mean maximal enhancement value of 35.61±8.32 Hu. In conclusion, familiarity with the CT findings and occupational environment exposure history will assist in earlier and easier diagnosis of pulmonary cryptococcosis in immunocompetent patients.

[Serial (18)F-FDG PET-CT imaging during radiotherapy for nasopharyngeal carcinoma: a prospective clinical study].

OBJECTIVE: The primary aim of this prospective study was to use serial (18)F-FDG PET-CT imaging to evaluate the trend of the tumor's maximum standardized uptake value (SUVmax) during radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC), and to explore the possibility of early evaluation of the tumor bio-metabolic response during radiotherapy. METHODS: Sixty patients with biopsy-proven primary NPC were prospectively enrolled into the study. All patients underwent four (18)F-FDG PET-CT scans: one initial scan before RT/cisplatin based concurrent chemoradiotherapy, at the point of 50 Gy during RT, the end of RT, and one month after RT, respectively. Tumor (18)F-FDG uptake was analyzed according to the World Health Organization pathological type. RESULTS: There was a significant difference (P < 0.001) of the mean of SUVmax of the primary site among pretreatment (11.20 ± 5.37) and posttreatment at the dose of 50 Gy (3.50 ± 1.59), at the end of RT (3.05 ± 1.56) and one month after RT (2.52 ± 1.46). There was also a significant difference (P < 0.001) of the mean of SUVmax of neck node site. However, there was a significant difference of the SUVmax between histological WHO type IIb and type IIa in the primary site (P = 0.046) [(67 ± 19)% reduction at dose 50 Gy for type IIb vs. (55 ± 24)% for type IIa] but not in the lymph nodes. CONCLUSIONS: Early PET scan during or right after RT instead of conventional 3 months interval after RT is indicated to evaluate the tumor response and to develop individualized adaptive radiotherapy in NPC. Our next study will attempt to demonstrate the results based on long-term follow-up data.

Biological response of nasopharyngeal carcinoma to radiation therapy: a pilot study using serial 18F-FDG PET/CT scans.

We used serial (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) to evaluate tumors' maximum standardized uptake value (SUV(max)) before, during, and after radiotherapy to explore the biological behavior of and response to radiation therapy in various subtypes of nasopharyngeal carcinoma (NPC). Sixty-one patients with pathologically diagnosed NPC were prospectively enrolled into the study. WHO type II(B) disease had a higher initial SUV(max) and more significant biological response at the primary site as compared with type II(A) subtype. The two subtypes of WHO type II NPC may significantly differ in their biological behavior and response to radiotherapy.