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PubMedDate not supplied

Yttrium-90 chelation properties of tetraazatetraacetic acid macrocycles, diethylenetriaminepentaacetic acid analogues, and a novel terpyridine acyclic chelator.

Realization of the potential of yttrium-90 for the radioimmunotherapy of cancer depends on rapid and kinetically stable chelation. Conditions were evaluated that influenced the chelation efficiency of these select chelators for yttrium-90: the macrocyclic chelators 2-(rho-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tet raacetic acid (nitro-DOTA); alpha-(2-(rho-nitrophenyl)ethyl)-1,4,7,10,- tetraazacyclododecane-1-acetic-4,7,10-tris(methylacetic) acid (nitro-PADOTA); 2-(rho-nitrobenzyl)-1,4,7,10-tetraazacyclotridecane- N,N',N",N"'-tetraacetic acid (nitro-TRITA); the acyclic chelator diethylenetriaminepentaacetic acid (DTPA); its analogues N-[2-amino-3-(rho-nitrophenyl)propyl]-trans- cyclohexane-1,2-diamine-N,N',N"-pentaacetic acid (nitro-CHX-A-DTPA) and 2-methyl-6-(rho-nitrobenzyl)-1,4,7- triazaheptane-N,N,N',N",N"-pentaacetic acid (nitro-1B4M-DTPA or nitro-MX-DTPA); and a novel acyclic terpyridine chelator, 6,6"-bis[[N,N,N",N"- tetra(carboxymethyl)amino]methyl]-4'-(3-amino-4-methoxyphenyl)-2,2':6',2 "- terpyridine (TMT-amine). The chelators fell into two distinct classes. The acyclic chelators, DTPA, nitro-CHX-A-DTPA, nitro-MX-DTPA, and TMT-amine, chelated instantaneously in a concentration-independent manner. Chelation efficiency was affected minimally when the concentrations of trace metal contaminants were increased. In contrast, the macrocyclic chelators, nitro-DOTA, nitro-TRITA, and nitro-PADOTA, chelated yttrium-90 more slowly in a concentration-dependent manner where efficiency was maximal only when the chelator:metal ratio was greater than 3. Their chelation efficiency diminished in a concentration-dependent fashion as the concentrations of trace metal contaminants were increased. Optimum labeling efficiencies were obtained through application of these principles.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1998

The effects of aluminum, iron, chromium, and yttrium on rat intestinal smooth muscle in vitro.

The modification of peristaltic activity in the presence of several metal ions has been investigated in the rat intestine by the isolated organ technique. The metals tested modify the intestinal movements: aluminum, chromium, and yttrium cause a decrease of amplitude, while iron showed no effect. By use of microscopic techniques, the presence of yttrium hydroxide was observed in the intestinal tissues. Iron also appears as a precipitate outside of the intestinal serosal, which may explain why iron did not modify the peristaltism. Chromium and aluminum were not apparent to microscope, despite being detected and quantified in the tissues by means of atomic emission spectrometer. We conclude that the trivalent ions of these elements may operate differently on the mechanisms of intestinal contractions: yttrium precipitates in intercellular spaces, iron precipitates outside the intestines, and chromium and aluminum remain in solution and are distributed homogeneously in the smooth intestinal muscle.

Aluminum↗
PubMed1991

Lithotripsy of gallstones by means of a quality-switched giant-pulse neodymium:yttrium-aluminum-garnet laser. Basic in vitro studies using a highly flexible fiber system.

The quality-switched neodymium:yttrium-aluminum-garnet laser represents a new instrument for athermal fragmentation of gallstones by transformation of optical energy into mechanical energy in the form of shock waves via local plasma formation. A highly flexible 300-micron fiber transmission system was used in basic investigations to determine the influence of varying pulse repetition rates (5-30 Hz) and pulse energies (15 and 20 mJ) on shock wave intensity and stone fragmentation in vitro for 105 biliary calculi of known size and chemical composition. After performance of 1200 shock wave pressure measurements using polyvinylidenefluoride hydrophones, stone fragmentation was analyzed by determination of fragment removal rates (volume of fragments removed per fragmentation time), ablation rates (mean volume removed per laser pulse), and median fragment sizes for each laser setting. With the quality-switched neodymium:yttrium-aluminum-garnet laser system, all concrements could be reliably disintegrated into small fragments (median diameter, 0.7-1.7 mm). Compared with pure cholesterol stones, a significantly higher fragment removal rate was achieved in cholesterol stones containing 30% calcium phosphate (P = 0.039), in cholesterol stones containing 20% pigment (P = 0.015), and in pure pigment stones (P = 0.007). Fragment removal rates, local shock wave pressures, and median grain sizes were significantly higher at a pulse energy of 20 mJ than with 15 mJ. Shock wave pressures showed a distinct dependence on pulse repetition rates at 20 mJ, yet not at 15 mJ. Because there is no evident hazard of thermal damage to tissue using the quality-switched neodymium:yttrium-aluminum-garnet laser, it appears to be a promising device for nonsurgical biliary stone therapy.

Aluminum↗
PubMed1990

Distribution, localization, and pulmonary effects of yttrium chloride following intratracheal instillation into the rat.

Metabolic behavior and pulmonary toxicity of yttrium chloride (YCl3) deposited in the lung was investigated. Yttrium chloride was instilled intratracheally into rats and the time-course and dose-related changes in distribution of Y between lung tissue and bronchoalveolar lavage fluid (BALF) and pulmonary inflammatory responses were investigated. Pulmonary clearance of Y was very slow and the half-life was estimated to be 168 days. Yttrium content in the supernatant of BALF did not exceed 5 micrograms Y/lung even when a dose of 200 micrograms Y/rat was administered, suggesting that the alveolar surface fluid could retain at most 5 micrograms Y. On the other hand, Y content in the pellet of BALF changed with the number of macrophages retrieved in BALF in both time-course and dose-response experiments. Transmission electron microscopy and X-ray microanalysis suggested that Y was localized in lysosomes of alveolar and interstitial macrophages, and basement membranes. These results clearly explain the long pulmonary half-life of Y. beta-Glucuronidase activity and calcium and phosphorous contents in the supernatant of BALF increased significantly even at the lowest dose (10 micrograms Y/rat). Comparative dose-effect profiles of lactate dehydrogenase activity in BALF supernatant revealed that 1 mol of YCl3 is equivalent to about one-third mole of cadmium compounds and about 3 mol of zinc oxide in the potency for acute pulmonary toxicity.

Animals↗
PubMed2005

Preparation and in vitro stability of (n,gamma) yttrium-90 hydroxyapatite.

Yttrium-90, produced by irradiating Y2O3 (15 mg) in the Pakistan Research Reactor (PARR-I) at a flux of approximately 1.5x10(14) neutrons/cm2/s, was used to prepare yttrium-90 hydroxyapatite particles for radiosynovectomy applications. The irradiated material was dissolved in concentrated hydrochloric acid, evaporated and taken up in distilled water. The 120 h irradiation resulted in the production of approximately 12GBq (324mCi) of 90Y at the end of irradiation (EOI) and the corresponding specific activity was approximately 1017GBq/g of yttrium. Hydroxyapatite (HA) particles were synthesized by an already reported method. Labeling of HA particles with 90Y was studied without a transchelating agent. Labeling yields of approximately 100% could be achieved with 40 mg of HA and 0.4 mg of 90Y. In vitro studies showed <2% loss of 90Y activity in normal saline and 1% human serum albumin solution over a period of 8 days. The high labeling yield, good stability and ease of preparation of the 90Y-HA particles indicate that these particles may find wide application in radiation synovectomy.

Drug Stability↗
PubMed2006

Yttrium-90 microspheres for the treatment of hepatocellular carcinoma: a review.

To present a critical review of yttrium-90 (TheraSphere) for the treatment of hepatocellular carcinoma (HCC). Medical literature databases (Medline, Cochrane Library, and CANCERLIT) were searched for available literature concerning the treatment of HCC with TheraSphere. These publications were reviewed for scientific and clinical validity. Studies pertaining to the use of yttrium-90 for HCC date back to the 1960s. The results from the early animal safety studies established a radiation exposure range of 50-100 Gy to be used in human studies. Phase I dose escalation studies followed, which were instrumental in delineating radiation dosimetry and safety parameters in humans. These early studies emphasized the importance of differential arteriolar density between hypervascular HCC and surrounding liver parenchyma. Current trends in research have focused on advancing techniques to safely implement this technology as an alternative to traditional methods of treating unresectable HCC, such as external beam radiotherapy, conformal beam radiotherapy, ethanol ablation, trans-arterial chemoembolization, and radiofrequency ablation. Yttrium-90 (TheraSphere) is an outpatient treatment option for HCC. Current and future research should focus on implementing multicenter phase II and III trials comparing TheraSphere with other therapies for HCC.

Carcinoma, Hepatocellular↗
PubMed2004

WGA-coated yttrium oxide beads enable an imaging-based adenosine 2a receptor binding scintillation proximity assay suitable for high throughput screening.

Adenosine receptors belong to the superfamily of G protein-coupled receptors and are involved in a variety of physiologic functions. Traditionally, binding assays to detect adenosine 2a (A2a) antagonists and agonists have used filtration methods that are cumbersome to run and not amenable to HTS. We developed scintillation proximity assays (SPA trade mark ) utilizing HEK293 RBHA2AM cell membranes, either wheat germ agglutinin (WGA)-coated yttrium silicate (YSi) or red-shifted yttrium oxide (YO) beads and the A2a-selective radioligand [(3)H]SCH 58261. Both beads gave windows (total binding/nonspecific binding) of >5 and K(d) values of 2-3 nM for the radioligand, in agreement with results obtained by filtration. In contrast, WGA-polyvinyltoluene as well as other bead types had windows of <3 and significant radioligand binding to the uncoated beads. A 384-well WGA-YO bead SPA was optimized utilizing a LEADseeker imaging system and an automated trituration process for dispensing the dense yttrium-based beads. Signals were stable after 4 h, and Z' values were 0.7-0.8. The LEADseeker imaging assay tolerated 2% dimethyl sulfoxide and generated IC(50) values of 3-5 nM for the A2a antagonist CGS 15943, comparable to that obtained by the filtration method. A number of adenosine and xanthine analogues were identified as hits in the Library of Pharmacologically Active Compounds (LOPAC). This imaging-based A2a SPA enables HTS and is a major improvement over the filtration method.

Adenosine A2 Receptor Agonists↗
PubMed1997

Persistent synovitis treated with radiation synovectomy using yttrium-90: a retrospective evaluation of 83 procedures for 45 patients.

The objectives were to investigate the efficacy and safety of yttrium-90 colloid (Y-90) synovectomy in joints with persistent synovitis and to examine the effect of a second synovectomy using a double dose after an initial inadequate response. Of the 45 patients at the University Hospital Utrecht who underwent Y-90 synovectomy between July 1987 and October 1995, the effectiveness and side-effects of all yttrium procedures (n = 83) were assessed retrospectively. Glucocorticoids were administered together with the yttrium, except in 1987. Radiation synovectomy had an overall success rate of 75% (complete or almost complete remission of synovitis) initially, i.e. within 1 month of the procedure, partly due to co-administration of glucocorticoids. However, in October 1995, only 17 joints (22%) were still in remission with a mean (S.D.) duration of remission of 20.8 months (22.0), range 1-95 months (median 16 months). In 60 joints (78%), synovitis was present at that time because of an unsatisfactory initial response to the Y-90 injection (19 joints) or recurrent synovitis during follow-up (41 joints); the mean (S.D.) duration of remission of these 60 joints was 3.3 months (5.9), range 0-22 months. A second injection of a double dose of Y-90 after an initial inadequate response (n = 8) did not contribute significantly to a better result. Short-term side-effects occurred in two cases after two Y-90 injections (2%) without glucocorticoid co-administration: a post-injection flare-up of synovitis and a local skin burn lesion. Persistent synovitis can be treated by Y-90 synovectomy with an overall success rate of 75% within 1 month. However, prolonged remission of synovitis is only achieved in 29% of joints with a good initial response. It does not appear worthwhile to perform a second synovectomy with a double dose if the initial response was inadequate. Y-90 synovectomy leads to only minor short-term side-effects (2%).

Adolescent↗
PubMed1995

Renal pathology after arterial yttrium-90 microsphere administration in pigs. A model for superselective radioembolization therapy.

RATIONALE AND OBJECTIVES: To test the selectivity of tissue damage in radioembolization, the authors performed an experimental study using superselective administration of yttrium-90 particles to deliver up to 100 Gy to the porcine kidney. Patterns and severity of damage in test organs were compared with controls, and the feasibility of this model is discussed. METHODS: Eight sows were included in the study. Bio-Rex 70 particles were applied via selective catheterization of the renal artery. Four pigs received inactive particles and four pigs received active particles. Organ distribution and shunting of yttrium-90 were determined, and kidney damage patterns were histologically analyzed. RESULTS AND CONCLUSIONS: The model demonstrates that yttrium-90-labeled resin particles can superselectively be applied. Retention of beta activity in the target organ was more than 95%. In addition to tissue shrinkage from mechanical obstruction, considerable damage ensued mainly by radiation-induced arterial necrosis and arteritis.

Animals↗
PubMed2004

Application of carbon dioxide and erbium:yttrium-aluminum-garnet lasers in inner ear surgery: an experimental study.

BACKGROUND: Surgery of the inner ear requires atraumatic techniques to preserve the sensory structures of the inner ear. With modern laser technology, surgery can be performed without mechanical contact, reducing the risk of direct mechanical trauma. However, energy transfer by laser light has the potential to induce damage by heating, pressure waves, or direct irradiation, depending on the properties of the laser and parameters of application. HYPOTHESIS: The application of laser systems in inner ear surgery may have an advantage over traditional techniques; the carbon dioxide laser in continuous mode with an automated scanning procedure and the erbium:yttrium-aluminum-garnet laser were compared with a mechanical technique, using a diamond drill. METHODS: A cochleostomy in the basal cochlear turn of guinea pigs was created. Thresholds in response to frequency-specific stimuli and clicks were established by recording compound action potentials, both before and after the procedure. RESULTS: The best results in terms of preservation of cochlear function were obtained with the diamond drill. However, a single ear had a complete loss after fracture of the cochlear wall. Mean threshold shifts observed with the carbon dioxide laser were slightly greater, showing mild high-frequency losses, although differences to the group of drilling were not statistically significant. Results with the erbium:yttrium-aluminum-garnet laser showed significantly higher degrees of hearing loss than the other two groups, predominantly in the high-frequency region. CONCLUSIONS: Mechanical opening of the inner ear using a microdrill can be performed with minimal hearing loss; however, it carries the risk of direct trauma to the inner ear. The carbon dioxide laser with a new scanning technology as a noncontact procedure is shown to be effective and safe. It can be regarded as a useful tool in inner ear surgery. The erbium:yttrium-aluminum-garnet laser has a greater potential to cause damage.

Aluminum↗
PubMed1983

Lack of rise in serum prolactin following yttrium-90 interstitial irradiation for acromegaly.

We have investigated the possibility that the increase in serum PRL levels observed in patients with acromegaly treated with external irradiation could be due to damage to the hypothalamus or portal vessels, by comparing the effects of yttrium-90 interstitial irradiation, which is highly localised and does not normally extend to the hypothalamus, in a similar series of patients. Sixteen acromegalic patients treated by interstitial irradiation with yttrium-90 are described; GH fell from a mean of 131 mU/l (median 113 mU/l) to 17 mU/l (median 8 mU/l) after one year (P less than 0.001). PRL fell in the five initially hyperprolactinaemic patients (mean fall +/- SD: 39 +/- 17 micrograms/l at one year), but remained unchanged in the normoprolactinaemic group; PRL responsiveness to TRH was retained. Five, out of the seven normoprolactinaemic patients examined, were shown by in vitro studies of their pituitary biopsies, to have tumours that also synthesised or secreted PRL. These results are consistent with the hypothesis that the rise in PRL following external irradiation is the result of damage to the hypothalamus or portal vessels. A less likely explanation is that an overgrowth of radio-resistant PRL-secreting tumour cells is occurring after external irradiation, but not after yttrium-90 implantation.

Acromegaly↗
PubMed1978

Intra-articular yttrium 90 in rabbits. Comparison of behaviour of various radiocolloids in rabbits and in man.

Comparative studies of the retention of various yttrium 90 radiocolloids and of noncolloidal yttrium 90 chloride were performed in rabbits with arthritis induced in one knee. Two colloids, the citrate and resin forms, showed a statistically significant difference in retention between inflamed and normal knees, isotope being retained better in the normal knee. Marked differences were found in the handling of the various yttrium preparations in rabbits compared with previously reported results in man. These differences suggest that the rabbit with induced arthritis is not a suitable model in which to test retention of different radiocolloids before use in man.

Animals↗
PubMed2000

Yttrium radiosynoviorthesis in the treatment of knee arthritis in rheumatoid arthritis: a systematic review.

OBJECTIVE: To consider the question: How strong is the evidence in favour of yttrium synovectomy in chronic knee arthritis in patients with rheumatoid arthritis in comparison with placebo and intra-articular steroid treatment? METHODS: A systematic review of the literature was performed using Medline and the Embase database. RESULTS: Initially, seven papers were identified, but only two met the inclusion criteria. Neither study showed evidence in favour of yttrium synovectomy. CONCLUSION: From the point of view of evidence based medicine it should be seriously questioned whether yttrium synovectomy deserves a place in clinical practice.

Arthritis, Rheumatoid↗
PubMed1991

Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01.

Radiolabeled antiferritin immunoglobulin (Ig) preparations were tested in patients with advanced, end-stage Hodgkin's disease. Four patients received indium-111 (111In)-labeled monoclonal antiferritin (QCI). Targeting was not observed in tumor-bearing areas. Instead, scans showed rapid accumulation of QCI in normal liver. Forty-five patients were injected with 111In-labeled polyclonal antiferritin (rabbit, pig, or baboon). Forty (89%) patients showed tumor uptake, with dosimetric estimates ranging from 300 to 3,000 cGy in 1 week for the subsequently administered yttrium-90 (90Y)-labeled antiferritin. Yttrium-labeled antibody caused hematologic toxicity. Treatment-induced toxicity was not observed in any other organ system. Intravenous autologous bone marrow cells, 18 days after the yttrium infusion, accelerated hematopoietic recovery in eight patients receiving 30 mCi or 40 mCi. Hematopoietic recovery after a 20 mCi 90Y-labeled antiferritin infusion was not influenced by an autologous bone marrow transplant. Two patients receiving 20 mCi and one patient receiving 50 mCi remained aplastic after transplantation for unknown reasons. In 29 assessable patients, a 62% response rate was observed; nine of the 18 responses were complete. Responses ranging from 2 to 26 months were more commonly noted in patients with small tumors and long disease histories. Dosimetric calculations did not predict for responses. Recurrences frequently occurred in new areas instead of areas exhibiting bulky disease at the start of the treatment. Complete responses after 90Y antiferritin were significantly (P less than .02) more frequent than in a previous study with iodine-131 (131I) antiferritin. Further improvements are needed to make this new treatment modality curative.

Adolescent↗
PubMed1981

Osmic acid versus yttrium-90 in rheumatoid synovitis of the knee.

The effectiveness of osmic acid and yttrium-90 in the treatment of synovitis of the knee in rheumatoid arthritis is compared in 126 patients followed-up for 3 years. Ninety-one knees were injected with osmic acid and eighty-four knees with yttrium-90. Osmic acid appeared to be more effective than yttrium-90 throughout the period of the follow-up but the difference only reached statistical significance (p less than 0.05) at 3 years. Both therapies were well tolerated by patients and should be considered as an alternative to operative synovectomy.

Aged↗
PubMed2004

Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin's lymphoma.

Targeted radiation therapy or radioimmunotherapy has been an important recent advance in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan, and the radiolabeled isotope yttrium 90. Yttrium 90 ibritumomab tiuxetan has been shown to be efficacious in the treatment of B-cell NHL. Initial phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and dose intensities in combination with chemotherapy and autologous or allogeneic stem cell transplantation in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas including mantle cell lymphoma, and chronic lymphocytic leukemia. This article reviews the ongoing trials with 90Y ibritumomab tiuxetan. Radioimmunotherapy has great promise, and the safe incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL.

Antibodies, Monoclonal↗
PubMedDate not supplied

What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres?

BACKGROUND/AIMS: The survival duration of patients with nonresectable hepatocellular carcinoma confined to the liver and treated with intraarterial yttrium-90 microspheres was highly variable. METHODOLOGY: Eighty-two patients treated by this method were analyzed. Thirty-one patients who lived for one year or longer from the date of first treatment were classified as 'long survivors' and 51 patients who died within 1 year were classified as 'short survivors'. RESULTS: Comparison between the 2 categories suggested that lower pretreatment level of alpha-fetoprotein and higher tumor-to-normal uptake ratio of yttrium-90 microspheres favored longer survival. Results also indicated that the treatment was effective even for large tumors and for postoperative recurrence. Repeated treatment of viable residual or recurrent tumors offered further palliation and prolongation of survival. CONCLUSIONS: Pretreatment alpha-fetoprotein level, tumor-to-normal uptake ratio of yttrium-90 microspheres and the number of treatments determine survival duration.

Adult↗
PubMed1975

Yttrium-90 citrate colloid for radioisotope synovectomy.

The preparation of an yttrium-90 citrate colloid is described. This formulation localizes in the synovial membrane and thereby eliminates any irradiation received by extra-articular tissues. Yttrium-90 is eluted from Sr-90 bound to a sulphonic acid ion exchange resin. The colloid is prepared using a 3:1 ratio of carrier yttrium and citrate. Contamination with ionic 90Y and ionic 90Sr was less than 1 percent and 0.001 percent, respectively. In the 28 patients studied, all of the injected dose of 90Y remained in the region of the joint. Brief clinical results are presented.

Animals↗