Kyung Bae Park

Self-expandable covered metallic esophageal stent impregnated with beta-emitting radionuclide: an experimental study in canine esophagus.

PURPOSE A specially designed self-expandable covered metallic stent impregnated with the beta-emitting radioisotope 166Ho (166Ho, energy: 1.85 and 1.76 MeV, T12: 26.8 h) was developed at our institute for the purpose of intraluminal palliative brachytherapy, as well as for treating malignant esophageal stricture and swallowing difficulty. The aim of this study was to evaluate the tissue response to brachytherapy and the safety of the radioactive metallic stent with regard to the normal canine esophagus before clinical application. METHODS AND MATERIALS 166Ho was impregnated into the polyurethane membrane (50 micron thickness) covering the outer surface of a self-expandable metallic stent (diameter, 18 mm; length, 40 mm). Stents with radioactivity 4.0-7.8 mCi (Group A, n = 15), 1.0-1.8 mCi (Group B, n = 5), and 0.5-0.7 mCi (Group C, n = 5) were placed in the esophagi of 25 healthy beagle dogs, and the stents were tightly anchored surgically to prevent migration. The estimated radiation dose calculated by Monte Carlo simulation was 194-383 Gy in Group A, 48-90 Gy in Group B, and 23-32 Gy in Group C. The dogs were killed 8-12 weeks after insertion of the stents, and histologic examinations of the esophageal walls were performed. RESULTS In Group A, 3 of 15 dogs died of wound infection, so specimens were obtained from only 12 dogs; all 12 cases showed esophageal stricture with mucosal ulceration. Microscopically, severe fibrosis and degeneration of the muscular propria were found in 3 dogs, complete fibrosis of the entire esophageal wall was found in 7 dogs, and esophageal fibrosis with radiation damage within periesophageal soft tissue was found in 2 dogs. However, esophageal perforation did not develop, despite extremely high radiation doses. In Group B, glandular atrophy and submucosal fibrosis were found, but the muscular layer was intact. In Group C, no histologic change was found in 3 dogs, but submucosal inflammation and glandular atrophy with intact mucosa were found in 2 dogs. CONCLUSIONS A radioactive, self-expandable covered metallic stent can be used as an alternative therapeutic modality for the palliative treatment of malignant esophageal stricture.

Phase II Study of Transarterial Holmium-166-Chitosan Complex Treatment in Patients with a Single, Large Hepatocellular Carcinoma

Purpose: Holmium-166 (166Ho) is a neutron-activated radioactive isotope whose effectiveness in hepatocellular carcinoma (HCC) was first reported in a preclinical study in 1991. Chitosan is a polymer of 2-deoxy-2-amino-D-glucose that readily forms a chelate with heavy metals and converts from a solution under acidic conditions into a gel under neutral or basic conditions. We performed a prospective trial of a transarterial administration of a radiopharmaceutical 166Ho-chitosan complex in patients with single, large HCC. Patients and Methods: The study involved 54 patients who had single HCC (≥3 cm) without a vascular shunt and were either inoperable or refused surgery. The 166Ho-chitosan complex was administered at a dose of 20 mCi per cm of tumor diameter (capping at 200 mCi) via the artery that directly fed the tumor. Results: The median tumor size was 5.3 cm (range: 3–13 cm). The response rate was 78% (42/54), and 31 patients had a complete response for a median duration of 27 months. The incidence of grade 3 or 4 leukopenia was 18.6%, anemia 7.4%, thrombocytopenia 27.8%, AST/ALT elevation 26%/24%, and total bilirubin elevation 5.6%. There were two treatment-related deaths (3.7%). Subset analysis revealed a substantial difference between the two groups categorized by tumor size (3–5 vs. >5 cm) with respect to response rate (p = 0.004) and overall survival (p = 0.02). Conclusion: We found that transarterial administration of the 166Ho-chitosan complex was highly effective in the treatment of HCC with acceptable toxicities, especially for patients with tumors of 3–5 cm.

Preparation of 153Sm-Chitosan Complex for radiation synovectomy

A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of chitosan and (153)SmCl(3). When a solution of this complex was injected into the knee joints of rabbits, minimal extra-articular leakage was observed. This can be attributed to the rapid change in the pH of the complex solution from acidic to neutral, resulting in the formation of gel followed by the subsequent retention in the administered site. Thus, the complex solution represents a promising candidate for radiation synovectomy.

Holmium-166-DTPA as a liquid source for endovascular brachytherapy

Liquid radiation sources with beta emitters have advantages of accurate positioning and uniform dose distribution to the vessel walls to prevent the restenosis of coronary artery. As a liquid radiation source, 166Ho-DTPA was prepared and evaluated its in-vivo pharmacokinetic behavior through animal studies.166Ho-DTPA was prepared by simple mixing the Holmium with DTPA at room temperature. The radiolabelling yield was 100% when the DTPA/Holmium molar ratio was >2. Radiolabelling of 166Ho-DTPA was not dependent on the pH range of 1.7-7.5. High radiochemical stability (>98%) was maintained over a period of 6 hours even with a radioactivity ( approximately 11.1 GBq/12 mg of DTPA) stored at room temperature. Biodistribution of 166Ho-DTPA in rats and gamma camera images in rabbits showed that 166Ho-DTPA was quickly excreted via the urinary system. The average of T(max) and T(1/2) of 166Ho-DTPA in the kidneys of rabbits were 3.71 +/- 1.18 min and 9.15 +/- 3.15 min. 166Ho-DTPA is a potential liquid radiation source for radiation brachytherapy to prevent the restenosis of the coronary artery using a liquid-filled balloon.

166Ho-coated balloon for vascular brachytherapy

A simple procedure was developed for coating the surface of a conventional percutaneous transluminal coronary angioplasty balloon angioplasty catheter with 166Ho. The absorbed dose delivered by the surface-coated catheter is twice that of a similar catheter filled with a solution containing the same activity of 166Ho. Leakage tests show that <0.6% of the coated activity is removable from the surface of the catheter. The coated catheter removes the risk of release of the 166Ho into the body as a result of rupture of the balloon, and also reduces the radiation exposure to staff.