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Introduction In patients with unresectable HCC, transcatheter arterial chemoembolization (TACE) is a widely used treatment. Recently, as an alternative treatment modality for HCC, transcatheter arterial embolization with radioisotopes has been investigated. In this study, we compared the therapeutic efficacy of an intra-hepatic arterial injection of Re-188-MN-16ET-lipiodol and the TACE method in rats with liver tumors. Methods Twelve male rats bearing hepatic tumors were divided into three groups to evaluate the efficacy of treatment (four in each group). Group 1 received an intra-hepatic arterial injection of 0.2 mCi of Re-188-MN-16ET-lipiodol; group 2 received epirubicin (0.5 mg/kg) and 0.1 ml of lipiodol emulsion; group 3 received 0.1 ml of normal saline and served as the control group. Tumor size was measured by liver sonography before injection, at two weeks, four weeks and eight weeks after injection. Survival time was calculated from the day of treatment to 56 days after treatment by the life-table method. The response to treatment and the survival time in each group were evaluated and compared. Results All rats treated with Re-188 MN-16ET-lipiodol showed good response to the therapy. Their tumor size decreased and all rats survived over eight weeks. All rats treated with epirubicin plus lipiodol survived over 8 weeks; however, two rats (50%) showed increased tumor size in the 8th week. As for the control group (rats treated with normal saline), all rats survived less than 37 days with continuous tumor growth. Conclusion Results showed that Re-188-MN-16ET-lipiodol can be a potential therapeutic pharmaceutical for the treatment of liver tumors.

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications through passive targeting tumor sites by enhanced permeability and retention effect. Radiolabeled liposomes have potential applications in radiotherapy and diagnostic imaging. The purpose of this study was to investigate the biodistribution, pharmacokinetics and imaging of nanotargeted (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (RBLPL) and unencapsulated (188)Re-BMEDA after intraperitoneal (ip) injection in a C26 colon carcinoma ascites mouse model. The nanopegylated liposomes were labeled with (188)Re-BMEDA. The labeling efficiency of RBLPL was 82.3+/-4.5%. In vitro stability of RBLPL in normal saline at room temperature and in rat plasma at 37 degrees C for 72 h was 92.01+/-1.31% and 82.4+/-1.64%, respectively. The biodistribution studies indicated that the radioactivity in ascites was 69.96+/-14.08 percentage injected dose per gram (% ID/g) at 1h to 5.99+/-1.97% ID/g at 48 h after ip administration of RBLPL. The levels of radioactivity in tumor were progressive accumulation to a maximum of 6.57+/-1.7% ID/g at 24 h. The radioactivity of (188)Re-BMEDA in ascites reached the maximum level of 54.89+/-5.91% ID/g at 1 h and declined rapidly with time. Pharmacokinetic studies revealed that the terminal half-life, total body clearance and area under the curve of RBLPL were 5.3-, 9.5- and 9.4-fold higher than that of (188)Re-BMEDA in blood, respectively. These results suggested that the long circulation, bioavailability and localization of RBLPL in tumor and ascites sites, which also demonstrate that the ip administration of RBLPL is a potential multifunctional nanoradiotherapeutics and imaging agents on a C26 colon carcinoma ascites mouse model.

Introduction Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N 2 S 2 tetradentate ligand, N -[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl]octadecanoate (H 3 MN-16ET), was introduced and labeled with 188 Re to create 188 Re-MN-16ET in the Lipiodol phase. The potential of 188 Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague–Dawley rats implanted with the N1S1 cell line. Methods Synthesis of H 3 MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of 188 Re-perrhenate and H 3 MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of 188 Re-MN-16ET/Lipiodol or 188 Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation. Results H 3 MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of 188 Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of 188 Re-MN-16ET in Sprague–Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with 188 Re-MN-16ET was quickly decreased from 9.15±0.23 (at 1 h) to 2.71%±0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that 188 Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55±1.44, 13.16±1.46 and 10.67%±0.95% of injected dose/g at 1, 24 and 48 h postinjection, respectively. The radioactivity in normal liver tissue was high but significantly lower than that of the tumors. Conclusion H 3 MN-16ET is a suitable tetradentate ligand for 188 Re labeling. From the animal data, we suggest that 188 Re-MN-16ET/Lipiodol has the potential to be a therapeutic radiopharmaceutical for hepatoma treatment.

Introduction Radioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, 188 Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl]-8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment. Methods Equimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA–trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA–trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of 188 Re-SOCTA–trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability. Results The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27±0.06 ( n =3). The complex could easily be labeled with 188 Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of 188 Re-SOCTA–trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA–trastuzumab and nonconjugated trastuzumab had similar binding capacity ( B max ) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that 188 Re-SOCTA–trastuzumab accumulated more intensively in the tumor site as compared to normal tissue. Conclusion We suggest that 188 Re-SOCTA–trastuzumab could be a potential candidate for radioimmunotherapy.

Radiolabeled Lipiodol has routinely been used in hepatoma therapy. In this article an attempt to develop a new 188 Re-ECD/Lipiodol radiopharmaceutical, in which the chelating agent ECD (ethyl cyteinate dimer), is the constituent of the known brain perfusion agent 99m Tc-ECD, and an evaluation of its stability and biodistribution in rats with hepatic tumors is presented. First, 188 Re-ECD was prepared in a vial, followed by extraction with Lipiodol to get the final product, 188 Re-ECD/Lipiodol. The optimal labeling conditions for 188 Re-ECD were: (1) tartaric acid which is better than EDTA as a weak chelating agent; and (2) 15 mg of SnCl 2 , as the reducing agent, and 5–10 mg of tartaric acid in each vial had a better labeling yield. The radiochemical purity of 188 Re-ECD/Lipiodol was more than 94%. Twenty-four male Sprague-Dawley rats with liver tumors were sacrificed at 1, 24, and 48 h (eight rats each time) after an injection of approximately 7.4 MBq of 188 Re-ECD/Lipiodol via the hepatic artery. The radioactivity in the liver tumor is significantly high following therapeutic arterial injection, and relatively low in other organs including the bone, spleen, brain, thyroid, stomach, muscle, blood, and testis throughout this study. In conclusion, the new preparation of 188 Re-ECD/Lipiodol is a candidate agent for the treatment of liver cancer.