Theranostics is a novel concept that combines diagnostics and therapeutics. In the field of diagnostics, various pieces of medical equipment are commonly used, such as X-ray computed tomography, magnetic resonance imaging, positron emission tomography, and sonography. Because of physical energy within these different pieces of equipment, ultrasound is a useful tool for theranostics, and it is particularly suitable for diagnostics with sonography and therapeutics with hyperthermia for cancer. Recently, microbubbles were recognized as an effective type of agent for imaging blood flow in tumors. In particular, Sonazoid, which is a commercially available microbubble, has been used for detection of hepatic tumors. In addition, microbubbles are useful tools for theranostics because they can be used not only as an ultrasound contrast imaging agent but also as an enhancer for hyperthermia with therapeutic ultrasound. To improve the accessibility of microbubbles in the deep tissue, researchers are developing various types of smaller bubbles such as the submicron-sized nanobubble. We have also developed novel liposomal bubbles (Bubble liposomes), which consist of entrapped perfluoropropane gas in a lipid bilayer. Bubble liposomes have several advantages over existing technologies, such as they can be used as ultrasound imaging agents, it is easy to modify the targeting molecules on their surfaces, and they are highly applicable for the enhancement of hyperthermia with therapeutic ultrasound. In summary, the combination of ultrasound and micro/nanobubbles would allow for the development of an ideal method for noninvasive theranostics. In this review, we will introduce recent developments on ultrasound theranostics using microbubbles and nanobubbles such as Bubble liposomes.

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Parthenolide (PTL), a nuclear factor-κB (NF-κB) inhibitor, has been known to have a significant thermo-enhancement effect. The purpose of this study is to report our clinical experiences of using PTL in perioperative period of transurethral microwave thermotherapy (TUMT) for the treatment of early prostate cancer and to compare the results with those of the patients who were treated in the similar manner without PTL administration. All the patients who underwent TUMT for early prostate cancer were pretreated with androgen deprivation therapy (ADT) at least for 3 months to reduce volume of the prostate to render the TUMT more effective. PTL, daily oral dose of 0.5 mg, was administered during the perioperative period of TUMT.
Forty-five patients with early prostate cancer, clinical stage T1c-T2cN0M0 were included in this study. Significant reduction in volume of the prostate (mean 34.6%) was noted after ADT for 3 months. Transurethral resection of the prostate in radical fashion was then performed at least 3 months after TUMT to wait for maturation of histopathologic changes of the prostate glands.
Thorough histopathologic study of all the transurethral resection of the prostate (TURP) chips revealed no cancer cell in 41 of 45 patients. Among 4 patients who were found to have remnant cancer cells in TURP chips, 1 was with non-viable cancer cells. Whereas, 3 were with probably viable cancer cells, but apparently degraded in malignancy. These results were apparently superior to those of the 75 patients who were treated in similar manner before administration of PTL. Analyses were performed using Student's t -test, chi-square test and Fisher's exact test and ANOVA.

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60 year-old male diagnosed cancer of esophagus with pulmonary metastasis who underwent hyperthermia twice a week, 269 times to the chest with chemotherapy. Though the primary lesion itself of esophagus was locally controlled, we gave Abraxane 100-300 mg every three weeks because the pulmonary metastasis gradually increased and upsized. The tumor remarkably shrank but we could not give further medication because of peripheral neuropathy (mainly numbness of feet), which was diagnosed Grade 3 of Common Terminology Criteria for Adverse Events (CTCAE). We heated the feet for 20 minutes using Thermotron-RF8. The subjective symptoms of the numbness of the feet reduced 40% by one heating, and CTCAE Grade 3 was reduced to Grade 2 by heating for 5 successive days. We report the above because there was no side effect such as skin burns but considerable feeling of heat during heating.

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