Objective: Antiangiogenesis therapy (AAT) has provided substantial benefits regarding improved outcomes and survival for suitable patients in clinical settings. Therefore, the early definition of therapeutic effects is urgently needed to guide cancer AAT. We aimed to optimize the early response monitoring and prediction of AAT efficacy, as indicated by the multi-targeted anti-angiogenic drug sunitinib in U87MG tumors, using noninvasive positron emission computed tomography (PET) molecular imaging strategies of multifactorial bioparameters.Methods: U87MG tumor mice were treated via intragastric injections of sunitinib (80 mg/kg) or vehicle for 7 consecutive days. Longitudinal MicroPET/CT scans with 18F-FDG, 18F-FMISO, 18F-ML-10 and 18F-Alfatide II were acquired to quantitatively measure metabolism, hypoxia, apoptosis and angiogenesis on days 0, 1, 3, 7 and 13 following therapy initiation. Tumor tissues from a dedicated group of mice were collected for immunohistochemical (IHC) analysis of key biomarkers (Glut-1, CA-IX, TUNEL, ανβ3 and CD31) at the time points of PET imaging. The tumor sizes and mouse weights were measured throughout the study. The tumor uptake (ID%/gmax), the ratios of the tumor/muscle (T/M) for each probe, and the tumor growth ratios (TGR) were calculated and used for statistical analyses of the differences and correlations.Results: Sunitinib successfully inhibited U87MG tumor growth with significant differences in the tumor size from day 9 after sunitinib treatment compared with the control group (P < 0.01). The uptakes of 18F-FMISO (reduced hypoxia), 18F-ML-10 (increased apoptosis) and 18F-Alfatide II (decreased angiogenesis) in the tumor lesions significantly changed during the early stage (days 1 to 3) of sunitinib treatment; however, the uptake of 18F-FDG (increased glucose metabolism) was significantly different during the late stage. The PET imaging data of each probe were all confirmed via ex vivo IHC of the relevant biomarkers. Notably, the PET imaging of 18F-Alfatide II and 18F-FMISO was significantly correlated (all P < 0.05) with TGR, whereas the imaging of 18F-FDG and 18F-ML-10 was not significantly correlated with TGR.Conclusion: Based on the tumor uptake of the PET probes and their correlations with MVD and TGR, 18F-Alfatide II PET may not only monitor the early response but also precisely predict the therapeutic efficacy of the multi-targeted, anti-angiogenic drug sunitinib in U87MG tumors. In conclusion, it is feasible to optimize the early response monitoring and efficacy prediction of cancer AAT using noninvasive PET molecular imaging strategies of multifactorial bioparameters, such as angiogenesis imaging with 18F-Alfatide II, which represents an RGD-based probe.

In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells. Western blot analysis revealed that Res-SLNs could promote the ratio of Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results indicate that the Res-SLN may have great potential for breast cancer treatment.

Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors. Therefore, the inhibition of MDK is considered a potential strategy for cancer therapy. In the present study, we demonstrate a novel small molecule compound (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, both of which are types of untreatable lung cancer. However, iMDK did not reduce the cell viability of MDK-negative A549 lung adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its specificity. iMDK suppressed the endogenous expression of MDK but not that of other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441 cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic administration of iMDK significantly inhibited tumor growth in a xenograft mouse model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic approach for the treatment of lung cancers that are driven by MDK.