Radiochemical Feasibility of Mixing of 99mTc-MAA and 90Y-Microspheres with Omnipaque Contrast.

Yttrium-90 (90Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (99mTc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution. In order to monitor the real-time implantation of the microspheres into the tumor, the 90Y microspheres could be suspended in omnipaque contrast for allowing visualization of the correct distribution of the microspheres into the tumor. The radiochemical purity of mixing 90Y-microspheres in various concentrations of omnipaque was investigated. The radiochemical purity and feasibility of mixing 99mTc-MAA with various concentrations of a standard contrast agent were also investigated. Results showed the radiochemical feasibility of mixing 90Y-microspheres with omnipaque is radiochemically acceptable for allowing real-time visualization of radioembolization under fluoroscopy.

Controlling injectability and in vivo stability of thermogelling copolymers for delivery of yttrium-90 through intra-tumoral injection for potential brachytherapy.

Intra-tumoral injection of radiopharmaceuticals such as yttrium-90 (90Y) or phosphorus-32 (32P) is an important route for brachytherapy in unresectable solid tumors such as locally advanced hepatocellular carcinoma. However, the injected radiopharmaceuticals can potentially leak out from the tumor site due to high intra-tumoral pressure. In this study, we demonstrated the use of thermogelling copolymers that can be injected into tumor and subsequently solidify as hydrogels within the tumor that can potentially overcome the above problem. To this end, a series of thermogelling polyurethane copolymers with varying compositions were designed and synthesized from Pluronic F127, poly(3-hydroxylbutyrate), and poly(propylene glycol), which were characterized in terms of their molecular structures, compositions, phase diagrams, rheological properties, and injectability and body temperature stability in vitro and in vivo. The analyses of our data elucidated the injectability of the copolymer solutions at low temperatures, and the stability of the hydrogels at the body temperature. This provided the basis on which we could identify one copolymer with balanced composition as the most suitable candidate for intra-tumoral injection and for prevention of the leakage. Finally, the injectability and in vivo stability of the copolymer solution and hydrogel loaded with 90Y were further demonstrated in a mouse tumor model, and the in vivo biodistribution of 90Y showed that the radionuclide could be retained at the tumor site, indicating that the 90Y-loaded copolymer has a great potential for tumor radio-brachytherapy.

Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

Upconversion nanoparticles as a contrast agent for photoacoustic imaging in live mice.

An inclusion complex of NaYF4 :Yb(3+) ,Er(3+) upconversion nanoparticles with α-cyclodextrin in aqueous conditions exhibits luminescence quenching when excited at 980 nm. This non-radiative relaxation leads to an unprecedented photoacoustic signal enhancement. In vivo localization of α-cyclodextrin-covered NaYF4 :Yb(3+) ,Er(3+) is demonstrated using photoacoustic tomography in live mice, showing its high capability for photoacoustic imaging.

Promising role of [18F] fluorocholine PET/CT vs [18F] fluorodeoxyglucose PET/CT in primary brain tumors-early experience.

Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality.

A novel approach to brachytherapy in hepatocellular carcinoma using a phosphorous32 (32P) brachytherapy delivery device--a first-in-man study.

PURPOSE: While potentially very useful, percutaneously delivered brachytherapy of inoperable intra-abdominal solid tumors faces significant technical challenges. This first-in-man study is designed to determine the safety profile and therapeutic efficacy of a novel phosphorous (32P) brachytherapy device (BrachySil) in patients with unresectable hepatocellular carcinoma. METHODS AND MATERIALS: Patients received single percutaneous and transperitoneal implantations of BrachySil under local anesthesia directly into liver tumors under ultrasound or computed tomographic guidance, at an activity level of 4 MBq/cc of tumor. Toxicity was assessed by the nature, incidence, and severity of adverse events (Common Toxicity Criteria scores) and by hematology and clinical chemistry parameters. Target tumor response was assessed with computed tomographic scans at 12 and 24 weeks postimplantation using World Health Organization criteria. RESULTS: Implantations were successfully carried out in 8 patients (13-74 MBq, mean 40 MBq per tumor) awake and under local anesthesia. Six of the 8 patients reported 19 adverse events, but no serious events were attributable to the study device. Changes in hematology and clinical chemistry were similarly minimal and reflected progressive underlying hepatic disease. All targeted tumors were responding at 12 weeks, with complete response (100% regression) in three lesions. At the end of the study, there were two complete responses, two partial responses, three stable diseases, and one progressive disease. CONCLUSION: Percutaneous implantation of this novel 32P brachytherapy device into hepatocellular carcinoma is safe and well tolerated. A significant degree of antitumor efficacy was demonstrated at this low dose that warrants further investigation.