Science to practice: are theranostic agents with encapsulated cells the key for diabetes therapy?

The transplantation of beta cells could be an effective therapy for diabetes, with much better stabilization of blood glucose levels than can be achieved with insulin injection. However, the therapeutic effect of these cell transplants usually lasts for a relatively short time owing to the strong immunologic reactions against the transplants. Protection from the immune system may be achieved by encapsulating the beta cells in such a way that their ability to release insulin is preserved. In the article of Arifi n and colleagues (1), encapsulated beta cells coembedded with DTDTPA (dithiolated diethylenetriaminepentaacetic acid) gadolinium­ coated gold nanoparticles are suggested as a biohybrid theranostic transplant. The in vitro and in vivo data presented in the article give hope that these transplants have the potential to solve many of the problems associated with beta cell treatment of diabetes. In this context, the visibility of the transplanted cells at computed tomography (CT), magnetic resonance (MR) imaging, and ultrasonography (US) might give the physician additional fl exibility in monitoring the transplantation procedure and its effectiveness over time. Furthermore, other cellular therapies may benefi t from cellular encapsulation. The combination of imaging of the biohybrid transplants and noninvasive functional assessment is likely to further improve assessment of the viability and function of the transplanted cells.

Molecular ultrasound imaging of early vascular response in prostate tumors irradiated with carbon ions.

Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1) and of alpha(v)beta(3)-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy) was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of alpha(v)beta(3)-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of alpha(v)beta(3)-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and alpha(v)beta(3)-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.