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PubMed1977

A clinical and prospective chromosomal study of yttrium-90 synovectomy.

Yttrium-90 synovectomy resulted in complete resolution of chronic knee synovitis in 40% of a group of 15 patients. These patients would have otherwise required surgical synovectomy. The number of chromosomal aberrations detected in 30 patients after yttrium-90 synovectomy showed a statistically significant increase over the pre-treatment analysis, and, following treatment, chromosomal damage was noted in nine patients who had no damage before treatment. The risk arising from this chromosomal damage is uncertain but, while the long-term implications of the chromosomal aberrations are investigated in those who have already been treated, this therapy should be reserved for the older patient.

Arthritis, Rheumatoid↗

PubMed1997

A retrospective review of yttrium-90 synovectomy in the treatment of knee arthritis.

We reviewed the case notes and X-rays of all patients with knee arthritis treated with yttrium-90 for the first time at a single institution from November 1981 to November 1995. Outcomes were assessed as 'improved' or 'not improved' by review of the case notes at 3, 6 and 12 months, and by the absence of further intra-articular (IA) steroid injections. Of the 121 knees treated, 87 had adequate follow-up information to allow an assessment of outcomes. Overall, 46% (95% CI 36-57) were improved at 12 months and 37% (95% CI 27-47) had no further IA injections (mean follow-up of 3.5 yr). Knees with osteoarthritis (OA) fared significantly worse with 10% (95% CI 0-29) vs 51% (95% CI 39-63) improved at 12 months (P < 0.05). Knees younger than 30 appeared to do better with 78% (95% CI 51-100) vs 28% (95% CI 17-45) having no further IA injections (P < 0.02). Knees with normal X-rays (Kellgren grade 0-1) did significantly better than those with more severe radiographic abnormalities (Kellgren grade 3-4), with 56% (95% CI 40-73) vs 24% (95% CI 8-40) improved (P < 0.01). Radiosynovectomy with yttrium-90 for knee arthritis appears to be of less value for patients with OA or with secondary OA changes on X-ray, and may be of more value for younger patients and those with spondyloarthropathies.

Adult↗

PubMed2001

Correlation of marrow dose estimates based on serial pretreatment radiopharmaceutical imaging and blood data with actual marrow toxicity in anti-CD20 yttrium-90 monoclonal antibody radioimmunotherapy of non-Hodgkin's B-cell lymphoma.

The purpose of this study was to investigate whether marrow radiation absorbed dose estimates predict haematotoxicity following radioimmunotherapy with an yttrium-90 labelled anti-CD20 monoclonal antibody in non-Hodgkin's B-cell lymphoma (NHL). Radiopharmaceutical data from 12 NHL radioimmunotherapy patients were analysed retrospectively using three methods of marrow radiation absorbed dose estimation based on serial pretreatment indium-111 labelled anti-CD20 monoclonal antibody activity versus time data (0-144 h): (i) lumbar spine (LS) image counts; (ii) blood clearance (BL); and (iii) whole body (WB) activity. Linear regressions were performed between the methods, and between each method and the 0-6 month post-treatment platelet and white blood cell count nadir and absolute drop in count (ADC). For the range of yttrium-90 activities (740-1547 MBq), absorbed dose estimates (mean +/- sigma) were: LS, 142+/-50 cGy (range 62-233 cGy); BL, 89+/-21 cGy (range 63-140 cGy); and WB, 54+/-10 cGy (range 36-63 cGy). The LS and BL marrow estimates differed significantly (P <0.003), with a correlation coefficient r of 0.36 (P = NS), while WB correlated significantly with both LS (r = 0.50, P < 0.05) and BL (r = 0.58, P < 0.05). The range of r with platelet nadir and ADC was -0.20 < or = r < or = 0.01, except for WB with ADC (r = 0.38) (all P = NS). Values of r for white blood cell nadir were unexpectedly positive, being 0.13 for BL and 0.29 for LS (P = NS), and 0.60 for WB (P < 0.025). Values of r for white blood cell ADC were 0.36 for BL and -0.26 for LS (P = NS), and 0.50 for WB (P < 0.05). These results indicate that different commonly employed methods of estimating marrow radiation absorbed dose may yield significantly differing results, which may not correlate with actual radiation toxicity. Therefore, caution must be exercised in relying on these results to predict haematotoxicity.

Algorithms↗

PubMed1992

Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor.

High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases.

Animals↗

PubMed1982

Treatment of acromegaly by trans-sphenoidal operation, 90-yttrium implantation and bromocriptine: results in 230 patients.

Two hundred and thirty patients with acromegaly were diagnosed and treated in a prospective cooperative study in twelve university clinics. Primary treatment was: trans-sphenoidal surgery (152 patients), trans-sphenoidal surgery with additional cryotherapy (eighteen patients), Yttrium-90-implantation (thirty patients), bromocriptine (thirty patients). The results of endocrine assessment before treatment and 6 months after operation, 90-Y implantation or commencement of bromocriptine therapy are reported. The best results (low GH, no or little deterioration of pituitary function, low complication rate) were achieved by trans-sphenoidal surgery, especially in patients with intrasellar tumours (basal GH less than 5 ng/ml in 59.7%). Results were less good with increasing tumour size. Additional cryosurgery was accompanied by a high rate of anterior pituitary insufficiency and is no longer employed. Yttrium-90-implantation resulted in less improvement in GH levels (basal GH less than 5 ng/ml in 51.7% of patients with intrasellar tumours), a high rate of pituitary insufficiency and more complications. Bromocriptine treatment was least effective in lowering GH concentrations (basal GH less than 5 ng/ml in 33% of patients with intrasellar tumours). Different criteria for treatment success were compared. In the entire group, basal GH concentrations below 5 ng/ml were attained in 51.7% of all patients whose values were higher than this prior to treatment. Suppressibility of GH below 2 ng/ml during glucose loading occurred in only 34.9%. An abnormal GH response to TRH/LHRH was present in 47.2% before and in 43.4% after/during treatment. The prognostic significance of this latter finding must be evaluated by further study.

Acromegaly↗

PubMed1992

Regression of liver metastases following treatment with yttrium-90 microspheres.

Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases. The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. Response to treatment was measured by serial estimations of carcino-embryonic antigen (CEA) and tumour volumes measured from serial computerized tomography (CT) scanning of the liver. There was a fall in the serum CEA level in all 26 patients in whom the serial estimations of CEA were performed following SIR therapy. The overall mean fall in CEA was 70% of pre-treatment levels with 88% of patients (23 of 26) experiencing more than a 50% fall in pre-treatment CEA levels. In 18 of 22 evaluable patients CT measured tumour volumes decreased following SIR therapy. In 48% of patients (10 of 22 patients) the decrease in tumour volume was more than 50%. SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer.

Adenocarcinoma↗

PubMed2003

Physical aspects of yttrium-90 microsphere therapy for nonresectable hepatic tumors.

Administration of yttrium-90 microspheres via the hepatic artery is an attractive approach to selectively deliver therapeutic doses of radiation to liver malignancies. This procedure allows delivering radiation absorbed doses in excess of 100 Gy to the tumors without significant liver toxicity. The microsphere therapy involves different specialties including medical oncology, radiation oncology, nuclear medicine, interventional radiology, medical physics, and radiation safety. We have treated 80 patients with nonresectable hepatic tumors with yttrium-90 microspheres during the past two years on an institutional study protocol. The nominal radiation absorbed dose to the tumor in this study was 150 Gy. Required activity was calculated based on the nominal radiation absorbed dose and patient's liver volume obtained from the CT scan, assuming a uniform distribution of the microspheres within the liver. Microspheres were administered via a catheter placed into the hepatic artery. The actual radiation absorbed doses to tumors and normal liver tissue were calculated retrospectively based on the patient's 99mTc-MAA study and CT scans. As expected, the activity uptake within the liver was found to be highly nonuniform and multifold tumor to nontumor uptake was observed. A partition model was used to calculate the radiation absorbed dose within each region. For a typical patient the calculated radiation absorbed doses to the tumor and liver were 402 and 118 Gy, respectively. The radiation safety procedure involves confinement of the source and proper disposal of the contaminated materials. The average exposure rates at 1 m from the patients and on contact just anterior to the liver were 6 and 135 uSv/h, respectively. The special physics and dosimetry protocol developed for this procedure is presented.

Brachytherapy↗

PubMed1979

An evaluation of repeat intra-articular injections of yttrium-90 colloids in persistent synovitis of the knee.

The effectiveness of a second intra-articular injection of yttrium-90 colloid was studied in 30 patients with persistent synovitis of the knee. All had responded poorly to a first injection of yttrium-90 yet seemed likely to benefit from this therapy. With a minimum review period of 6 months complete remission of synovitis was obtained in 20%, while 63% gained symptomatic relief, with some reduction of synovitis. No improvement occurred in 17%, and in this group generalised disease activity was more apparent.

Colloids↗

PubMed1979

Evaluation of two regimens to immobilise the knee after injections of yttrium-90.

Two regimens to immobilise the knee after injection were compared in patients receiving intra-articular yttrium-90 for persistent synovitis of the knee, the patients being randomly allocated to receive either complete bed rest or full mobilisation with the affected knee in a firm splint. There was no difference in the percentage of the radioisotope retained in the knee or in that taken up by other tissues between the two regimens. It is concluded that after intra-articular injections of yttrium-90 strict bed rest in hospital is unnecessary.

Bed Rest↗

PubMed2002

Grain growth in nanocrystalline yttrium-stabilized zirconia thin films synthesized by spin coating of polymeric precursors.

This article reports results of experimental studies on the microstructural evolution of nanocrystalline yttrium-stabilized zirconia thin films synthesized on a Si substrate via a polymeric precursor spin-coating approach. Grain growth behavior has been investigated at different annealing temperatures (700-1200 degrees C) for periods of up to 240 h. A similar film thickness (approximately 120 nm) was maintained for all of the samples used in this study, to avoid variation in film thickness-dependent grain growth. The effects of the thermal history of the film and the annealing atmosphere on the grain growth were also studied. A simple semiempirical grain growth model has been developed to describe isothermal annealing data and to predict dynamic grain growth behavior during the sintering of polymeric precursor layers to form cubic-phase nanocrystalline yttrium-stabilized zirconia films.

Air Pressure↗

PubMed2004

Metastatic breast cancer in a 54-year-old woman: integrative treatment with yttrium-90 radioembolization.

In 1993, a 54-year-old woman was diagnosed with early-stage breast adenocarcinoma and treated with doxorubicin and cyclophosphamide followed by tamoxifen. Nine years later, the patient presented for integrative treatment, with liver metastases. Carcinoembryonic antigen was significantly elevated. The patient was started on a heavily fractionated, multiple-agent chemotherapy regimen; however, she underwent significant adverse effects and the treatment was suspended. She then started on intravenous nutrition along with specific nutritional supplements. Two months later, a similar chemotherapeutic regimen was started in association with her existing nutritional protocol. One month later, the carcinoembryonic antigen began to rise, and a positron emission tomography scan was ordered that revealed the persistence of multiple and extensive liver metastases as well as possible skeletal metastases. The patient was started on an oral bisphosphonate and referred to interventional radiology for consultation on radioembolization with yttrium-90. After being accepted for treatment, the patient under-went a right hepatic lobe angiogram and radioembolization. Within 2 weeks, she realized significant improvements in her clinical and laboratory status; chemotherapy was discontinued. She later underwent radioembolization to her left lobe. Thirteen months after the yttrium-90 treatment, the patient remains on an integrative program with radiographically and clinically stable disease.

Adenocarcinoma↗

PubMed2006

Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: a case report.

Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemo-embolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.

Adult↗

PubMed2002

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma.

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 ((131)I), tositumomab, and yttrium 90 ((90)Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Morphology of yttrium-90 treated experimental arthritis].

A rheumatoid arthritis was produced in rabbits according to the method described by Klinge. It was treated with a single dosage of 2 mCi Yttrium-90. After 3 weeks the animals treated with Yttrium showed less fibrosis of the synovial membrane than the controls. After 6 weeks the synovial membrane of the non-treated controls showed considerable fibrosis but the synovial villi of the treated animals were slender and largely unchanged.

Animals↗

PubMed2002

A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).

Adenocarcinoma↗

PubMed2003

[Effect of the long-term intake of yttrium in drinking water on trace elements in F1 generation mice].

The effects of the long-term intake of yttrium on trace elements in tissues and yttrium in brain of F1 generation mice were studied so as to elucidate some physiological function of the rare earths. The mice were fed with Y3+ (0, 23.25 mg/L, 2325.00 mg/L) dissolved water at different levels for seven months. The level of trace elements such as Cu, Cd, Pb and Y in brain and Se in brain, liver, spleen and kidney of F1 generation mice were measured by ICP-MS and atom fluorescent method. The results showed that, compared with control mice, significant changes in content of Se (P < 0.05) in spleen and Y (P < 0.05) in brain were observed, but no changes were found in content of Pb, Cd, and Cu in brain for the high dose group, and an increase was detected in content of Se(P < 0.05) in spleen for the low dose group, suggesting that long-term intake of Y3+ might enhance the absorption of Se in some tissue that might be one of the biological effect of rare earth and, Y3+ might enter young mammalian brain.

Animals↗

PubMed2004

Use of Yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

Aged↗

PubMed2005

Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model.

PURPOSE: Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 ((90)Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD45 ((131)I-anti-CD45) antibody biodistribution in humans. EXPERIMENTAL DESIGN: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of (90)Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of (90)Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of (90)Y-anti-CD45 antibody was then compared with that previously obtained with (131)I-anti-CD45 antibody in macaques. RESULTS: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of (90)Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Yttrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with (131)I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. CONCLUSIONS: This study shows that (90)Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the (131)I immunoconjugate in the same animal model.

Animals↗