Update on the development of molecular imaging and nanomedicine in China: Optical imaging.

Molecular imaging has received increased attention worldwide, including in China, because it offers noninvasive characterization of widely diverse clinically significant pathologies. To achieve these goals, nanomedicine has evolved into a broad interdisciplinary field with flexible designs to accommodate and concentrate imaging and therapeutic payloads into pathological cells through selective binding to disease specific cell membrane biomarkers. This concept of personalized medicine reflects the vision of "magic bullets" proposed by German biochemist Paul Ehrlich over 100 years ago. As happening worldwide, Chinese scientists are contributing to this tsunami of science and technologies through impactful national programs and international research collaborations. This review provides a comprehensive update of Chinese innovations to address intractable unmet medical need in China and worldwide in the optical sciences. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging.

Folate receptor-targeted 19 F MR molecular imaging and proliferation evaluation of lung cancer.

BACKGROUND: Folate receptors (FRs) hold great potential as important diagnostic and prognostic biological marker for cancer. PURPOSE: To assess the targeted capability of the FR-targeted perfluorocarbon (PFC) nanoparticles and to assess in vivo the relationship between FR expression and tumor proliferation with fluorine-19 (19 F) MR molecular imaging. STUDY TYPE: Prospective animal cancer model. ANIMAL MODEL: H460 (n = 14) and A549 (n = 14) nude mice subcutaneous tumor models. FIELD STRENGTH: 9.4T, 1 H and 19 F RARE sequences. ASSESSMENT: Intracellular uptake of the PFC nanoparticles was tested in H460 and A549 cell lines. 19 F MRI of H460 and A549 subcutaneous tumors was performed following intravenous injection of PFC nanoparticles. The concentration of PFC in tumors were compared. 3'-Deoxy-3'-18 F-fluorothymidine (18 F-FLT) positron emission tomography / computed tomography (PET/CT) imaging, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were performed to confirm tumor proliferation. STATISTICAL TESTS: One-way or two-way analysis of variance. P < 0.05 was considered a significant difference. RESULTS: The diameter of the FR-targeted nanoparticles was 108.8 ± 0.56 nm, and the zeta potential was -58.4 ± 10.8 mV. H460 cells incubated with FR-targeted nanoparticles showed ∼59.87 ± 3.91% nanoparticles-labeled, which is significantly higher than the other groups (P < 0.001). The PFC concentration in H460 tumors after injection with FR-targeted nanoparticles was 4.64 ± 1.21, 8.04 ± 1.38, and 9.16 ± 2.56 mmol/L at 8 hours, 24 hours, and 48 hours, respectively (P < 0.05 compared to others). The ratio of 18 F-FLT uptake for H460 and A549 tumors was 3.32 ± 0.17 and 1.48 ± 0.09 (P < 0.05), and there was more Ki-67 and PCNA in H460 tumor than A549. DATA CONCLUSION: 19 F MRI with FR-targeted PFC nanoparticles can be used in differentiating of FR-positive and FR-negative tumors, and further, in evaluation of the two cancer models proliferation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1617-1625.

Melatonin synergized with cyclosporine A improves cardiac allograft survival by suppressing inflammation and apoptosis.

Melatonin, a widespread physiological mediator, has been demonstrated to exhibit a dose­dependent immunoregulatory effect in vitro and in vivo, including mediating physiological circadian rhythms, neutralizing free radicals and exerting antisenescence actions. In the present study, the efficacy and mechanism of melatonin alone or in combination with cyclosporine (CsA) in prolonging heart transplantation survival was examined. Daily treatment with melatonin (200 mg/kg/day) through a gavage, significantly prolonged the survival of cardiac grafts (mean survival time, 13.4±2.4 days; n=7; P<0.0001) compared with the untreated controls (5.8±1.2 days; n=7). When CsA (5 mg/kg/day) was co­administered with melatonin (50 mg/kg/day), the survival rate improved (31.6±2.4 days; n=7; P<0.001), compared with that achieved by only 20 mg/kg/day CsA (22±2.8 days; n=7). As expected, melatonin significantly alleviated the inflammatory response and apoptosis as determined by TdT­mediated dUTP­biotin nick end labeling assay (P<0.05). Further analysis demonstrated that melatonin significantly reduced p65 activation and the release of inflammatory factors. Therefore, these findings indicate that melatonin in combination with CsA protected the cardiac allograft by inhibiting inflammation­induced apoptosis. These results provide evidence for a novel therapeutic approach for future immunosuppressive agents in organ transplantation.

Prognostic analysis for survival after resections of localized primary cardiac sarcomas: a single-institution experience.

BACKGROUND: Primary cardiac sarcomas are rare diseases with a poor prognosis. This study aims to provide a prognostic analysis after different levels of resections of cardiac sarcomas. METHODS: Twenty-nine patients undergoing resections of primary cardiac sarcomas at the Zhongshan Hospital from September 1995 to July 2012 were retrospectively reviewed. RESULTS: There were 15 women and 14 men. The mean age was 41.0 years. The most common histologic type was angiosarcoma (28%). The median survival for the entire cohort was 17 months (range, 5 to 216 months). Patients with microscopically negative margin (R0) resections had a better median survival than those with microscopically positive margin (R1) resections (58 months versus 11 months; p<0.001). The median survival after an R1 resection was not different from that after a partial resection (12 months; p=0.81). The median local recurrence-free survival after an R0 resection was longer than that after an R1 resection (36 months versus 6 months; p<0.001). Five patients who underwent R0 resections and repeated resections of local recurrences or metastases had the longest median survival of 72 months. None of the patients with R0 resections received adjuvant therapy. Multimodality treatment after R1 and partial resections slightly increased the survival. CONCLUSIONS: For nonmetastatic and localized primary cardiac sarcoma, an R0 surgical resection of cardiac sarcomas should be performed. Aggressive surgical treatment or radiation therapy for local recurrence or metastasis prolongs the survival. Multimodality treatment is recommended after incomplete resections of cardiac sarcomas. The role of adjuvant chemotherapy after R0 resections is unclear.

[Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells].

OBJECTIVE: To study the methods and mechanisms of immune tolerance in cardiac transplantation. METHODS: Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation. RESULTS: The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro. CONCLUSIONS: Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.