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Histological study of effects of colloidal 90 yttrium on knee joint tissues of rabbits.

The administration of 0-2-0-4 mCi 90 yttrium (90Y) into a normal rabbit knee joint fails to induce medical synovectomy and results in the proliferation of the synovialis. The synovial mesothelium shows early radiation damage but subsequently follows a restitution of the whole. Later (within 4 to 16 weeks) an extensive fibrosis of the stratum synovialis develops, as well as an occlusion and sclerosis of smaller synovial vessels and capillaries. These changes explain the beneficial therapeutic effect of 90Y in a chronic inflammatory joint effusion. After irradiation that joint cartilage shows an increased cellular proliferation of the superficial tangential cells and in the vicinity of the cruciate ligaments small foci of degenerated cartilage are present. The overall pattern of a joint treated with intra-articular 90Y corresponds to the histological pattern encountered regularly in joints of older people. Changes of the cartilage after the 90Y radiation could represent a factor predisposing the treated joint to a subsequent development of osteoarthrosis.

Animals↗

Effect of intra-articular inj-ction of radioactive colloids of erbium and yttrium on the growth of rabbit legs.

The effect of the intra-articular injection of radioactive erbium 169 and yttrium 90 on the growth of the leg in rabbits has been studied. I colloid state these isotopes are used clinically for synovial ablation. These beta emitters slow down bone growth in proportion to the amount of radioactivity injected. If the joint has previously been damaged by an inflammatory arthritis the effect of the radiation on the bone growth is reduced.

Animals↗

Effect of yttrium 90 on experimental allergic arthritis in rabbits.

Seventeen rabbits were immunized with complete Freund's adjuvant and bovine serum albumin by the method of Dumonde and Glynn (1962), as modified by Cooke and Jasin (1972). Fifteen weeks after allergic arthritis developed in the knee joint, 8 animals were given an injection of 20 muCi yttrium 90 (90Y) into the left joint cavity; 7 were injected with 400 muCi. The animals were sacrificed at 2, 4, 8, 12, and 16 weeks and at 6 and 12 months after the injection. The right knee joint served as control for assessment of untreated allergic arthritis. Morphological control of the severity of the arthritis was provided by sacrificing 2 uninjected animals 13 weeks after immunization.

Animals↗

Distribution of yttrium 90 ferric hydroxide colloid and gold 198 colloid after injection into knee.

Thirteen knees were injected with yttrium 90(90Y) ferric hydroxide colloid, and 12 with gold 198(198Au) colloid for treatment of persistent synovitis. Retention in the knee and uptake in lymph nodes and liver were measured by a quantitative scanning technique. There was no significant difference in the retention in the knee of the two different colloids. A tendency towards higher lymph node uptake was observed with 198Au compared with 90y. The inflammatory activity of the knee at the time of treatment may have influenced the subsequent lymph node uptake of 198Au, but not that of the 90Y, nor the overall leakage of either from the knee. 90Yferric hydroxide colloid was retained in the treated knee at least as well as other colloids which have been used for this purpose.

Gold Colloid, Radioactive↗

Radioactivity studies on 2 synovial specimens after radiation synovectomy with yttrium-90 silicate.

Synovial membranes surgically removed from the knees of 2 patients who had received radioactive yttrium-90 silicate have been examined. Autoradiographs showed that in both cases the activity was unevenly distributed over the synovium. One of the specimens, removed 7 weeks after administration of the isotope, was found to contain a slight degree of radioactivity, attributable in part to a long-lived radioactive contaminant.

Arthritis, Rheumatoid↗

Treatment of pigmented villonodular synovitis of the knee with yttrium-90 silicate: prospective evaluations by arthroscopy, histology, and 99mTc pertechnetate uptake measurements.

The diffuse form of pigmented villonodular synovitis of eight knee joints of eight patients was treated by intra-articular injection of 185 MBq yttrium-90 silicate (90Y). Six patients had a recurrence of disease after one or two surgical synovectomies. After treatment with 90Y once or twice four knees showed clinical improvement with an accompanying decrease of the inflammatory activity as measured by the technetium-99m pertechnetate (99mTcO4-) uptake ratio and the severity of the diseased synovial tissue. Arthroscopy was performed before and six months after each 90Y treatment. The ratio of 99mTcO4- uptake in the inflamed compared with the normal knee joint correlated well with the macroscopical grading of pigmented villonodular synovitis. In all cases areas of persistent synovitis were found after the 90Y injection and this was confirmed both by histological examination and 99mTcO4- uptake measurements. Biopsy specimens taken from the diseased synovial areas showed histologically mostly less prominent and less numerous villi. The cartilage damage was slightly increased in only two cases. No radiological deterioration was found during follow up (mean 24 months, range 12-41). No complications of the radiosynoviortheses were noted.

Adolescent↗

Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies.

Two yttrium-90 (90Y) radiosynovectomy procedures were compared. One procedure, performed at the Royal Perth Rehabilitation Hospital (RPRH) required a shorter immobilisation time than that performed at the Sir Charles Gardiner Hospital (SCGH). There were no significant differences in outcome between the two procedures for the groups with inflammatory and osteoarthropathy. Thirty two patients (45 joints) with inflammatory arthropathy were treated (25 with rheumatoid arthritis, three with psoriatic arthritis, two with ankylosing spondylitis, and two with unspecified inflammatory arthropathy) and 40 patients (58 joints) with osteoarthropathy. A separate assessment of local lymph node spread in patients treated by the RPRH showed a minor spread of 90Y in one of 37 joints assessed. A marked improvement in the patient evaluation scores in the inflammatory arthropathy group at three months persisted at 12 months. Good lasting responses were more common in patients with inflammatory arthropathy with a normal joint or early radiological disease. A marked improvement in the pain and evaluation scores occurred at three months in the group with osteoarthropathy but had disappeared by six months after treatment.

Arthritis, Psoriatic↗

Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198.

Eight patients with Nelson's syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.

Adenoma↗

Feasibility of outpatient management after intra-articular yttrium-90: comparison of two regimens.

In a study comparing two regimens of treatment after intra-articular irradiation of the knee with yttrium-90 one group of patients was allocated to bed rest for 48 hours in hospital and the other to mobilisation at home. Initially a Robert-Jones orthopaedic bandage was applied to the knee in all patients, serving as a semi-rigid splint, but as loss of isotope from the knee was appreciable in the mobilised patients, subsequent patients were sent home with the knee in a plaster-of-Paris cylinder. No difference in extra-articular spread or chromosomal damage was found between the patients sent home with their knee in a rigid splint and those treated by bed rest. Clinical outcome at three months was satisfactory in all three groups. These results show that rigid splinting is essential in reducing extra-articular spread of the isotope but that bed rest is not necessary. Increases in intra-articular pressure associated with quadriceps muscle activity combined with flexion of the knee may be the most important factor affecting extra-articular spread of isotope.

Ambulatory Care↗

Successful treatment of Cushing's disease using yttrium-90 rods.

Interstitial irradiation using yttrium-90 (90Y) rods implanted by needle into the pituitary gland was used as primary treatment in 16 patients with pituitary dependent Cushing's disease. Clinical and biochemical remission was observed within three or six months in 13 and in the remaining three after a supplementary implant. There was no perioperative morbidity. Follow-up from the time of definitive operation ranged from six to 123 months (mean 39). No recurrence has been observed. The return of a normal diurnal cortisol rhythm has been observed in 10/12 patients studied after remission. Some form of long-term pituitary hormone replacement therapy was required in only the six patients who had received the largest irradiation dose. Implantation of 90Y is safe and effective treatment for patients with Cushing's disease, comparing favourably with selective trans-sphenoidal pituitary surgery.

Adolescent↗

Optic chiasm enhancement associated with giant aneurysm and yttrium treated pituitary adenoma.

A patient with a history of pituitary tumour treated with yttrium 29 years before presented with an asymmetrical chiasmal neuropathy. Magnetic resonance imaging showed a partially thrombosed giant aneurysm of the right internal carotid artery, with enhancement of the chiasm and right optic tract adjacent to the aneurysm. It was thought that, in addition to the effects of compression, a peri-aneurysmal inflammatory reaction had developed, causing breakdown of the blood-brain barrier and consequent inflammatory changes in the optic chiasm. High dose steroid treatment led to significant improvement in vision within two weeks. Steroids may have a role in the acute preservation of vision in similar cases, as well as in cases of deterioration following coiling or embolisation of aneurysms where thrombosis within the aneurysm has been induced.

Adenoma↗

Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications.

Management of hepatic malignancies is a ubiquitous medical problem. Surgical resection of primary or metastatic liver cancer, with or without adjuvant chemotherapy, is the most effective method for enhancing survival; however, hepatic malignancies in the vast majority of patients are unresectable both at initial manifestation and at recurrence. In these patients, palliative cytoreductive therapies may help to retard tumor progression and therefore favorably alter the course of the disease. Since hepatic neoplasms are principally supplied by the hepatic artery, various arterially delivered cytotoxic agents have been developed to achieve these objectives. Recently, the Food and Drug Administration approved the transarterial administration of yttrium-90 microspheres for liver-directed therapy. Effective use of these devices requires knowledge of the accumulated clinical experience and a dedicated multidisciplinary effort to ensure optimal outcomes and avoid therapy-specific life-threatening complications.

Adult↗

A single treatment of yttrium-90-labeled CHX-A"-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice.

Antitumor diabody molecules are noncovalent single-chain Fv dimers that recapitulate the divalent binding properties of native IgG antibodies. Diabodies are capable of substantial accumulation in tumor xenografts expressing relevant antigens in immunodeficient mouse models. With a Mr of approximately 55,000, diabodies are rapidly cleared from the circulation, resulting in tumor-to-blood ratios that significantly exceed those achieved early after the administration of monoclonal antibodies. We have evaluated the therapeutic potential of the beta-emitting isotope yttrium-90 (t1/2, 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tumor-associated antigen. We have found that a single intravenous dose of 150 microCi (200 microg) 90Y-CHX-A"-C6.5K-A diabody substantially inhibits the growth rates of established MDA-361/DYT2 human breast tumor xenografts in athymic nude mice. In contrast, 300 microCi (300 microg) 90Y-CHX-A"-C6.5K-A diabody resulted in only a minor delay in the growth of SK-OV-3 human ovarian cancer xenografts. The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy.

Animals↗

Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors.

Bombesin receptors are overexpressed on a variety of human tumors like prostate, breast, and lung cancer. The aim of this study was to develop radiolabeled (Indium-111, Lutetium-177, and Yttrium-90) bombesin analogues with affinity to the three bombesin receptor subtypes for targeted radiotherapy. The following structures were synthesized: diethylenetriaminepentaacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH1) and 1,4,7,10-tetraazacyclododecane-N,N',N",N"' -tetraacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH2). [111In]-BZH1 and in particular [90Y]-BZH2 were shown to have high affinity to all three human bombesin receptor subtypes with binding affinities in the nanomolar range. In human serum metabolic cleavage was found between beta-Ala11 and His12 with an approximate half-life of 2 hours. The metabolic breakdown was inhibited by EDTA and beta-Ala11-His12 (carnosine) indicating that carnosinase is the active enzyme. Both 111In-labeled peptides were shown to internalize into gastrin-releasing peptide-receptor-positive AR4-2J and PC-3 cells with similar high rates, which were independent of the radiometal. The biodistribution studies of [111In]-BZH1 and [111In]-BZH2 ([177Lu]-BZH2) in AR4-2J tumor-bearing rats showed specific and high uptake in gastrin-releasing peptide-receptor-positive organs and in the AR4-2J tumor. A fast clearance from blood and all of the nontarget organs except the kidneys was found. These radiopeptides were composed of the first pan-bombesin radioligands, which show great promise for the early diagnosis of tumors bearing not only gastrin-releasing peptide-receptors but also the other two bombesin receptor subtypes and may be of use in targeted radiotherapy of these tumors.

Animals↗

Comparison of carbon dioxide and neodymium: yttrium-aluminum-garnet lasers in surgery of the inferior turbinate.

At the Department of Otorhinolaryngology-Head and Neck Surgery of the University of Kiel, 533 patients with hyperplastic inferior turbinates were treated between 1987 and 1994 with various carbon dioxide (CO2) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser techniques. We report on the therapeutic results of both types of laser turbinectomy and compare their long-term results with those of submucosal diathermy. Among the different techniques, we preferred the following approaches. The CO2 laser technique involved the application of a few laser spots (laser energy density 6,100 J/cm2 per lesion) to the head of the turbinate under the operating microscope. In the Nd:YAG laser procedure, diffuse, low-power irradiation (laser energy density < 53 kJ/cm2) of the entire concha was performed under endoscopic control. The CO2 laser procedure involved little bleeding and hardly any pain. It produced a positive effect after only a few days and required no follow-up treatment. The success of Nd:YAG laser treatment, by contrast, only became evident after weeks or months, due to the slow scarring process. Compared to submucosal diathermy, both laser methods produced better long-term results. Two years postoperatively, the overall success rate, as defined by patient satisfaction, was 79.6% for the CO2 laser, 68.3% for the Nd:YAG laser, and 36% for submucosal diathermy.

Adult↗

Matrix assessment of the articular cartilage surface after chondroplasty with the holmium:yttrium-aluminum-garnet laser. A long-term study.

A long-term in vivo study was performed to assess biochemical changes after laser repair of articular cartilage. Forty New Zealand White rabbits were sacrificed 26 weeks after undergoing an articular cartilage chondroplasty with use of a holmium:yttrium-aluminum-garnet laser at 0.8 joules per pulse and a rate of 10 Hz. Glycosaminoglycan content in the repaired tissue decreased significantly with both perpendicular (19.59+/-5.6 microg hexosamin/mg of dry tissue) and tangential delivery (14.78+/-4.5 microg/mg) compared with the sham-treated tissue (39.6+/-5.0 microg/mg). Cellular viability was also significantly decreased. Sulfate incorporation was decreased to 203+/-142 cpm/mg of dry cartilage in the tangential mode and 461+/-209 cpm/mg in the tangential mode, compared with the sham at 1845 cpm/mg. Uptake of [3H]thymidine decreased to 463+/-473 cpm/mg of dry tissue and 455+/-170 cpm/mg in the tangential and perpendicular modes, respectively, compared with 2465 cpm/mg in the sham tissue. There were no significant differences between the tangential and perpendicular delivery modes in any assessments performed. The shortterm chondrocyte destruction previously noted in a 12-week study after laser treatment was not reversed during a longer-term 26-week study, and cellular viability was not recovered, suggesting that the loss of chondrocyte function may be permanent.

Aluminum Silicates↗

Holmium: yttrium aluminium garnet laser lithotripsy for symptomatic Kock pouch calculi.

Kock first described continent ileostomy for fecal diversion in 1969 as an alternative procedure to conventional ileostomy. Later, this procedure was replaced by restorative proctocolectomy with ileal pouch anal anastomosis as the procedure of choice. The main reasons for its virtual abandonment include technical difficulty, high morbidity, and the need for a stoma. To our knowledge, this report is the first published case of successful enterolith destruction and retrieval from a Kock pouch, using a Holmium: yttrium aluminium garnet laser. This outpatient procedure can avoid the morbidity and cost of a laparotomy.

Aluminum↗

Radioimmunotherapy for non-Hodgkin's lymphoma with yttrium 90 ibritumomab tiuxetan.

The increasing incidence of non-Hodgkin's lymphoma (NHL), coupled with the lack of optimal treatment options, has prompted the development of novel treatments. Of these, radioimmunotherapy is one of the most promising. Two of the radiolabeled monoclonal antibody therapies being studied in the treatment of NHL are yttrium 90 (90Y) ibritumomab tiuxetan and iodine 131 (131I) tositumomab. The radionuclides 90Y and 131I emit beta radiation; 131I also emits gamma radiation, thus requiring more elaborate precautionary measures to limit radiation exposure. The monoclonal antibody portions of the drugs target the CD20 surface antigen that is present on the majority of B-cell lymphomas, resulting in direct radiation to the targeted cells, as well as indirect targeting of adjacent cells (known as the crossfire effect). Clinical trials of 90Y ibritumomab tiuxetan in patients with NHL have produced promising results. The safe and effective use of radioimmunotherapy requires a multidisciplinary team approach in which nurses play a central role.

Antibodies, Monoclonal↗