Quantitatively tracking engraftment of intracerebrally or intravenously transplanted stem cells and evaluating their concomitant therapeutic efficacy for stroke has been a challenge in the field of stem cell therapy. In this study, first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized for quantitatively tracking mesenchymal stem cells (MSCs) transplanted intracerebrally or intravenously into stroke rats, and then the therapeutic efficacy of MSCs delivered by both routes and the possible mechanism of the therapy are evaluated. It is demonstrated that (125)I-fSiO4@SPIOs have high efficiency for labeling MSCs without affecting their viability, differentiation, and proliferation capacity, and found that 35% of intracerebrally injected MSCs migrate along the corpus callosum to the lesion area, while 90% of intravenously injected MSCs remain trapped in the lung at 14 days after MSC transplantation. However, neurobehavioral outcomes are significantly improved in both transplantation groups, which are accompanied by increases of vascular endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor of metalloproteinases-3 in blood, lung, and brain tissue (p < 0.05). The study demonstrates that 125I-fSiO4@SPIOs are robust probe for long-term tracking of MSCs in the treatment of ischemic brain and MSCs delivered via both routes improve neurobehavioral outcomes in ischemic rats.

Gold nanoparticles (AuNPs) have recently garnered great interest as potential radiosensitizers in tumor therapy. However, major challenges facing their application in this regard are further enhancement of tumor accumulation of the particles in addition to enhanced permeability retention (EPR) effect and an understanding of the optimal particle size and time for applying radiotherapy after the particle administration. In this study, we fabricated novel cyclic c(RGDyC)-peptide-conjugated, Gd- and 99 mTc-labeled AuNPs (RGD@AuNPs-Gd99 mTc) probes with different sizes (29, 51, and 80 nm) and evaluated their potential as radiosensitization therapy both in vitro and in vivo. We found that these probes have a high specificity for αvβ3 integrin positive cells, which resulted in their high cellular uptake and thereby enhanced radiosensitization. Imaging in vivo with MRI and SPECT/CT directly showed that the RGD@AuNPs-Gd99 mTc probes specifically target tumors and exhibit greater accumulation within tumors than the RAD@AuNPs-Gd99 mTc probes. Interestingly, we found that the 80 nm RGD@AuNPs-Gd99 mTc probes exhibit the greatest effects in vitro; however, the 29 nm RGD@AuNPs-Gd99 mTc probes were clearly most efficient in vivo. As a result, radiotherapy of tumors with the 29 nm probe was the most potent. Our study demonstrates that RGD@AuNPs-Gd99 mTc probes are highly useful radiosensitizers capable of guiding and enhancing radiation therapy of tumors.

Hepatic VIC showed significant correlation with R2* and MR-measured LIC (r = 0.885 and 0.871, respectively; P < .0001). To differentiate among different LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg of iron per gram of dry tissue, the corresponding optimal cutoff values for VIC were 2.50, 5.13, 8.93, and 17.97 HU, respectively. At a LIC threshold of 7.0 mg of iron per gram of dry tissue or higher, 100% sensitivity (15 of 15 patients) and 100% specificity (19 of 19 patients) were obtained for VIC. There was no significant difference between VIC and R2* (area under the ROC curve, 0.964 vs 0.993, respectively; P = .299) in grading LIC levels at a LIC threshold of 3.2 mg of iron per gram of dry tissue or higher. Conclusion Hepatic VIC is a potential index for accurately evaluating and grading clinically significant liver iron accumulation, with a diagnostic performance similar to that of MR imaging.