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PubMed2006

Thermodynamic study of lanthanide(III) complexes with bifunctional monophosphinic acid analogues of H4dota and comparative kinetic study of yttrium(III) complexes.

New bifunctional H(4)dota-like ligands with three acetic acid and one phosphinic acid pendant arms and propionate (H(5)do3ap(PrA)) or 4-aminobenzyl (H(4)do3ap(ABn)) reactive groups bound to the phosphorus atom were investigated. Potentiometric studies showed that the ligands have a similar basicity to the parent H(4)dota and the stability constants of their complexes with sodium(i) and selected lanthanide(III) ions are also similar. Formation and acid-assisted decomplexation kinetics of yttrium(III) complexes with a series of H(4)dota-like ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert complex is that with H(4)do3ap(ABn). Rates of complexation and decomplexation can depend on the ability to transfer proton(s) outside/inside the complex cavity and, therefore, on the hydrophobicity of the ligands. The results demonstrate that the new bifunctional ligands are suitable for labelling biomolecules with yttrium(iii) radioisotopes for utilization in nuclear medicine.

Journal Article↗
PubMed2001

Microstructure, toughness and flexural strength of self-reinforced silicon nitride ceramics doped with yttrium oxide and ytterbium oxide.

Self-reinforced silicon nitride ceramics with additions of either yttrium oxide or ytterbium oxide have been investigated at room temperature after various processing heat treatments. Devitrification of the intergranular phase in these materials is very sensitive to the heat treatment used during processing and does not necessarily improve their strength and toughness. Hot-pressed ceramics without a subsequent devitrification heat treatment were the strongest. The ytterbium oxide-doped silicon nitride ceramics were consistently tougher, but less strong, than the yttrium oxide-doped silicon nitride ceramics. In all the ceramics examined, the fracture toughness showed evidence for R-curve behaviour. This was most significant in pressureless sintered ytterbium oxide-doped silicon nitride ceramics. A number of toughening mechanisms, including crack deflection, bridging, and fibre-like grain pull-out, were observed during microstructural analysis of the ceramics. In common with other silicon nitride-based ceramics, thin amorphous films were found at the grain boundaries in each of the ceramics examined. Arrays of dislocations left in the elongated silicon nitride grains after processing were found to belong to the {101;0}<0001> primary slip system.

Journal Article↗
PubMed2003

Lithium and sodium yttrium orthosilicate oxyapatite, LiY9(SiO4)6O2 and NaY9(SiO4)6O2, at both 100 K and near room temperature.

Lithium yttrium orthosilicate oxyapatite [lithium nonayttrium hexakis(silicate) dioxide], LiY(9)(SiO(4))(6)O(2), crystallizes in the centrosymmetric space group P6(3)/m at both 295 and 100 K. The structure closely resembles those of fluorine apatite and sodium yttrium orthosilicate oxyapatite [sodium nonayttrium hexakis(silicate) dioxide], NaY(9)(SiO(4))(6)O(2), which was also investigated, at 270 and 100 K, in this study. There are two different crystallographic sites for the Y(3+) ion, which are coordinated by seven and nine O atoms. One-fourth of the nine-coordinated site is occupied by Li or Na atoms, thus maintaining charge balance. The Si atom occupies a tetrahedral site. The two compounds show no symmetry change between room temperature and 100 K, and the alterations in structural parameters are small.

Journal Article↗
PubMed1992

Percutaneous obliteration of the cystic duct with a holmium:yttrium-aluminum-garnet laser: results of in vitro and animal experiments.

OBJECTIVE: The purpose of this study was to investigate the feasibility of using a holmium:yttrium-aluminum-garnet laser to permanently occlude the cystic duct in order to isolate the gallbladder from the biliary-enteric circulation and prevent gallstone formation. MATERIALS AND METHODS: To determine the optimal laser parameters (power and pulsing rate) for cystic duct thermocoagulation, 20 freshly excised porcine gallbladders with intact cystic ducts underwent low-energy (0.075-0.085 J/pulse) or high-energy (0.20-0.25 J/pulse) thermocoagulation. Histopathologic examination was done to determine the extent of cystic duct injury. After in vitro experiments, percutaneous transcholecystic laser thermocoagulation of the cystic duct was performed on 23 anesthetized domestic pigs (four controls). Cholangiograms immediately after laser thermocoagulation were obtained to assess cystic duct occlusion. Animals were sacrificed for histopathologic correlation immediately after laser thermocoagulation (n = 4), 72 hr later (n = 4), and 6 weeks later (n = 15). RESULTS: In the in vitro studies, all 10 cystic ducts in the high-energy group were occluded, while only four in the low-energy group were occluded. At histology, all cases in both groups showed circumferential injury to the cystic duct wall without injury to the cystic artery or vein. In the in vitro experiments, the cystic duct was successfully cannulated in 21 (91%) of 23 animals. Cholangiography after thermocoagulation showed occlusion of the cystic duct in 16 (84%) of 19 cases. Immediately after laser thermocoagulation, the cystic duct mucosa was circumferentially destroyed, whereas after 72 hr necrosis of the cystic duct wall and periductal tissues had occurred. By 6 weeks, all pigs had complete cystic duct fibrosis without injury to the common bile duct. CONCLUSION: Holmium:yttrium-aluminum-garnet laser thermocoagulation of the cystic duct can be performed easily, results in immediate cystic duct occlusion, and leads to permanent fibrous ductal obliteration by 6 weeks.

Animals↗
PubMed2002

Use of a neodymium:yttrium-aluminum-garnet laser to remove exuberant granulation tissue from the esophagus of a horse.

Use of a neodymium:yttrium-aluminum-garnet laser to remove exuberant granulation tissue from the esophagus of a horse A 4-year-old Quarter Horse mare was evaluated because of recurrent esophageal obstruction. Endoscopic examination revealed a proliferative mass in the esophagus approximately 55 cm aborad to the nares. Histologic examination of biopsy specimens revealed diffuse suppurative esophagitis and granulation tissue with no evidence of neoplasia. The mass was excisedand ablated transendoscopically with a neodymium:yttrium-aluminum-garnet laser. During a follow-up examination 2 weeks after the final laser procedure, the mass was no longer apparent, and the esophagus appeared healed. Six months after the final examination, there had been no recurrence of the mass. In this horse, transendoscopic laser excision was efficacious and avoided problems associated with an esophagotomy.

Animals↗
PubMed1989

Neodymium:yttrium-aluminum-garnet laser vaporization for palliation of obstructing esophageal carcinoma.

Palliative therapy for obstructing esophageal carcinoma is more often necessary than curative surgery. The neodymium:yttrium-aluminum-garnet laser was used for vaporization of obstructing esophageal carcinoma in 18 patients requiring 24 treatments. Three women and 15 men (age range 42 to 87 years) had esophageal carcinoma (seven squamous cell and nine adenocarcinoma). Twelve tumors were at the esophagogastric junction, four at the midesophagus, and two in the cervical esophagus. Lengths varied from 3 to 7 cm. Inoperability was due to diffuse metastases in eight patients, local invasion in five, poor operative risk in one patient, and patient refusal for operative treatment in four patients. Energy use was 1000 to 22,600 J per session (mean 6120 J). Good results were achieved in 16 patients (88.9%): Seven returned to full diet, five to soft diet, and four to full fluids without dysphagia. Four patients required retreatment 1 to 3 months later because of recurrent dysphagia. One patient was not benefited by the treatment and died of carcinomatosis 1 week later. No intraoperative complications occurred. Postoperatively, one patient had laryngeal edema and another had a bronchoesophageal fistula 3 weeks later. The mean survival time is 3 1/2 months. Neodymium:yttrium-aluminum-garnet laser vaporization for obstructing esophageal carcinoma is effective palliation regardless of histologic tumor type. It can be performed under direct vision with a low frequency of postoperative complications.

Adenocarcinoma↗
PubMed1996

Use of the holmium yttrium aluminum garnet laser for percutaneous thoracolumbar intervertebral disk ablation in dogs.

OBJECTIVE-To evaluate a laser ablation-technique for treatment of thoracolumbar intervertebral disk disease in dogs. DESIGN-Prospective case series. ANIMALS-33 dogs with signs of recurrent back pain associated with intervertebral disk disease after the initial episode had been managed conservatively for a minimum of 2 weeks. PROCEDURE-Spinal needles were placed percutaneously through the annulus fibroses to permit delivery of an optical fiber into the nucleus pulposes of thoracolumbar intervertebral disks T10-11 through L3-4. Fluoroscopy was used to guide needle placement. Holmium yttrium aluminum garnet laser energy then was used to ablate the contents of each selected intervertebral disk. Intervals from time of treatment to time of assessment ranged from 3 to 114 weeks. RESULTS-All dogs recovered without complication. Results of follow-up radiography and histologic evaluation indicated that percutaneous holmium yttrium aluminum garnet laser ablation reduces the volume of nucleus pulposus in treated disks. CLINICAL IMPLICATIONS-Used as a clinical treatment and prophylactically, this minimally invasive procedure should prevent further extrusion of partially herniated disks and should reduce the chances of subsequent herniation of disks at other treatment sites.

Animals↗
PubMed1993

Re-evaluating the need for hospitalization following synovectomy using Yttrium-90 silicate.

In 51 patients treated with Yttrium-90 (Y-90) synovectomy for rheumatoid (inflammatory) arthritis (IA) and OA of the knee we found that decreased retained knee activity (RKA) and increased extra-articular activity in lymph nodes and liver are more likely to be found in IA than OA and following bilateral knee injections. Joint inflammation, as assessed by radionuclide blood pool scan but not by SF white cell count, correlates with decreased RKA and increased activity in lymph nodes. Intra-articular steroid had no significant effect on retention or extra-articular uptake. Strict hospital immobilization improves RKA of Y-90 in IA but not in OA. Y-90 synovectomy in OA shows good RKA and low extra-articular uptake. We recommend strict immobilization following Y-90 synovectomy, particularly in IA patients and/or those with high joint blood flow.

Adult↗
PubMed1975

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.

Adenoma↗
PubMed1975

Acute knee joint rupture after yttrium 90 injection.

Two cases of acute rupture of the knee joint are reported after the intra-articular injection of radioactive yttrium 90. It is suggested that this may be a complication of intra-articular radioactive injections.

Arthritis, Rheumatoid↗
PubMed1993

Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis.

OBJECTIVES: The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. METHODS: The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. RESULTS: A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. CONCLUSION: Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.

Adolescent↗
PubMed1987

Therapy of peritoneal carcinomatosis of human colon cancer xenografts with yttrium 90-labeled anti-carcinoembryonic antigen antibody ZCE025.

The present study was undertaken to determine whether an anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAB), labeled with the potent beta emitter yttrium 90, could alter the growth of diffuse intraperitoneal carcinomatosis of colon cancer. Nude mice bearing the CEA-producing human tumor line LS174T received therapy with the anti-CEA MAB ZCE025 90Y. Animals were evaluated 12 days after therapy. Untreated animals had a mean (+/- SEM) tumor burden of 3.99 +/- 0.10 g, while animals treated with ZCE025 90Y had 0.29 +/- 0.04 g present. This decrease was significant compared with the 1.31 +/- 0.16 g of tumor present in animals treated with a 90Y-labeled nonspecific antibody 96.5c. The therapeutic effects seen with ZCE025 90Y suggest a potentially useful role for 90Y-labeled anti-CEA MABs in the treatment of gastrointestinal carcinomatosis.

Animals↗
PubMed1989

Prolongation of survival of nude mice bearing human colon cancer. Treatment with yttrium 90-labeled anti-carcinoembryonic antigen antibody.

Nude mice bearing diffuse intraperitoneal carcinomatosis of the human colon cancer cell line LS174T were treated with an anti-carcinoembryonic antigen monoclonal antibody (MAB) that was labeled with yttrium 90 (90Y-ZCE025). Control animals were either untreated or treated with nonspecific 90Y-MAB (90Y-96.5c). The median survival (MS) for untreated animals was 26 days. The MS for specific and nonspecific therapy that consisted of 120 microCi of 90Y-MAB was 69 and 34 days, respectively. No significant improvement in the MS was observed with a second 120-microCi administration of 90Y-MAB given two weeks later. A decreased MS was observed with 80 microCi of 90Y-MAB given every four days for three cycles. In each category, specific therapy had a significant advantage over nonspecific therapy in increased effectiveness and decreased toxicity. The 90Y-ZCE025 therapy gave an increased life span of almost 200%. The therapeutic effects with different dosing regimens have important implications for treatment planning.

Animals↗
PubMed1997

Advantage of yttrium-90-labeled over iodine-131-labeled monoclonal antibodies in the treatment of a human lung carcinoma xenograft.

BACKGROUND: The purpose of this investigation was to compare the therapeutic effectiveness of yttrium-90 (90Y)-labeled monoclonal antibodies (MoAbs) with iodine-131 (131I)-labeled MoAbs delivered to human tumor xenografts at their maximum tolerated doses (MTD). METHODS: Nude mice bearing size-matched human lung adenocarcinoma xenografts (Calu-3) with mean tumor dimensions of approximately 0.8 cm received intravenous injections of the MTD of either 90Y- or 131I-labeled MoAbs. The mice received 125 microCi of 90Y-RS11 or 90Y-RS7, or 300 microCi of 131I-RS11 or 131I-RS7. Tumor size was measured weekly. Body weight and blood counts were monitored to measure toxicity. RESULTS: The calculated average radiation doses delivered to tumors in mice treated with 90Y-RS11 and 90Y-RS7 were 3578 and 3787 centigray (cGy), respectively, versus 1264 and 1368 cGy for 131I-RS11 and 131I-RS7, respectively. These values were calculated taking into consideration the tumor size-dependent absorbed fractions for the beta particles of both radioisotopes. The calculated radiation doses absorbed in the tumor correlated with the tumor responses observed. Mean tumor volume decreases at nadir were 66% and 87% after 90Y-RS11 and 90Y-RS7 therapy, respectively, with 15 of 30 mice treated with either MoAb having complete regression of their tumors. In contrast, only mean stable disease was observed with the 131I MoAb treatments. CONCLUSIONS: The results demonstrate the superiority of 90Y-labeled MoAbs over conventionally labeled 131I-labeled MoAbs for therapy in this model. The fact that a substantial percentage of complete remissions was achieved with 90Y-labeled MoAbs suggests a considerable radiosensitivity of the tumor studied, and supports the suitability of choosing this tumor type as an attractive target for future clinical radioimmunotherapy.

Animals↗
PubMed1989

Effect of yttrium-90-labeled anti-carcinoembryonic antigen monoclonal antibody on the morphology and phenotype of human tumors grown as peritoneal carcinomatosis in athymic mice.

Grossly visible peritoneal carcinomatosis resembling that seen in man was produced in athymic mice 7 days after intraperitoneal injection of 8 x 10(5) cells of the carcinoembryonic antigen (CEA)-producing human colon carcinoma cell line LS174T. The mice received intraperitoneal injections of 40 to 160 microCi of yttrium-90 (90Y)-labeled anti-CEA monoclonal antibody (MAb). When the mice were killed 12 days after injection, a significant inhibition of tumor growth, ranging from 40% to 95%, was observed in the treated animals when compared to the growth of tumors in the untreated animals (P less than 0.001). No mortality secondary to the therapy was seen. The bone marrow was depleted significantly at the higher doses of labeled MAb, but total recovery was observed 4 weeks after treatment. Histologically, the treated tumors showed extensive radiation effects early in the posttherapy period and massive necrosis at later times. Minute foci of viable tumor remained in the periphery. New tumor outgrowths with histologic features similar to those in the untreated controls began to appear 3 weeks after therapy. The CEA expression of the treated tumors was similar to that of the untreated controls during the early posttreatment period, diminishing progressively as the tumors became necrotic. Newly grown tumor nodules in the treated animals lacked significant CEA expression both initially and at later times. Our studies suggest that therapy with 90Y-anti-CEA MAb therapy results in selection of tumor clones lacking CEA, and that a single large dose of 90Y-MAb should be more effective than multiple fractions of smaller doses.

Animals↗
PubMed1992

A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma.

METHODS: Ten patients with primary hepatocellular carcinoma were treated with intraarterial instillation of yttrium-90 (Y-90) microspheres, including eight men and two women (median age, 52 years; range, 29-69 years). Four patients were treated at a targeted hepatic dose of 50 Gy, two at 75 Gy, and four at 100 Gy. RESULTS: In 8 of the 10 patients, there was a significant concentration of Y-90 in localized tumor masses with tumor-to-liver perfusion ratios from 1.0:1-10.0:1. No patient had a complete or partial response, but 10 patients had stable disease (median duration, 10 weeks; range, 5-64 weeks). The median survival was 18 weeks (range, 2-150 weeks), and three patients lived longer than 1 year. Significant bone marrow or hepatic toxicity was not seen. One patient had a radiation-induced duodenal ulcer that required surgical management. CONCLUSIONS: Intraarterial instillation of Y-90 microspheres appears to be safe and deserves additional evaluation to determine whether there is meaningful activity in patients with primary hepatocellular carcinoma.

Adult↗
PubMed1993

An experimental study and clinical pilot trials on yttrium-90 glass microspheres through the hepatic artery for treatment of primary liver cancer.

BACKGROUND: Yttrium-90 (90-Y) glass microsphere is a new kind of radiation microsphere for internal radiation therapy of primary liver cancer (PLC). The study was carried out by administration of 35 microns nondegradable 90-Y glass microsphere through the hepatic artery for treatment of PLC. METHODS: Six rabbits were injected with 185-1480 megabecquerels (MBq) of 90-Y glass microspheres, and three rabbits were injected with 35-300 mg of 89-Y glass microspheres for the toxic test. Eighteen patients received 2442-5550 MBq of 90-Y glass microspheres for the treatment of PLC. Whole blood counts, liver function, and imaging examination were performed. Pathologic examinations were performed on all rabbits. RESULTS: All rabbits were apparently well after absorbing 114.1-845.2 Gy 90-Y glass microspheres in the liver but showed transient degeneration of hepatocytes and portal fibrosis histologically. The mean absorbed dose in liver tissue of patients with PLC was 30.33 Gy, whereas that in tumor tissue was 88 Gy and the highest in tumor tissue, 186.36 Gy. The mean tumor:liver tissue ratio was 3:1; the highest, 14:1. Fourteen patients were still alive after half a year's follow-up and 6 of these 14 were still alive after 1 year. CONCLUSIONS: The rabbits could tolerate up to eight-fold of the upper limit of clinical dose (100 Gy). Good responses to the radiation therapy of 90-Y glass microspheres in patients with localized and hypervascular or vascular mass were achieved. Contraindications for the therapy were presence of massive hepatic arterioportal shunt and cancer emboli in the main portal vein. It is safe and applicable to deliver 90-Y glass microspheres in large doses through the hepatic artery for internal radiation treatment of PLC.

Adult↗