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Planar gamma camera imaging and quantitation of yttrium-90 bremsstrahlung.

UNLABELLED: Yttrium-90 is a promising radionuclide for radioimmunotherapy of cancer because of its energetic beta emissions. Therapeutic management requires quantitative imaging to assess the pharmacokinetics and radiation dosimetry of the 90Y-labeled antibody. Conventional gamma photon imaging methods cannot be easily applied to imaging of 90Y-bremsstrahlung because of its continuous energy spectrum. METHODS: The sensitivity, resolution and source-to-background signal ratio (S/B) of the detector system for 90Y-bremsstrahlung were investigated for various collimators and energy windows in order to determine optimum conditions for quantitative imaging. After these conditions were determined, the accuracy of quantitation of 90Y activity in an Alderson abdominal phantom was examined. RESULTS: When the energy-window width was increased, the benefit of increased sensitivity outweighed degradation in resolution and S/B ratio until the manufacturer's energy specifications for the collimator were exceeded. Using the same energy window, we improved resolution and S/B for the medium-energy (ME) collimator when compared to the low-energy, all-purpose (LEAP) collimator, and there was little additional improvement using the high-energy (HE) collimator. Camera sensitivity under tissue equivalent conditions was 4.2 times greater for the LEAP and 1.7 times greater for the ME collimators when compared to the HE collimator. Thus, the best, most practical selections were found to be the ME collimator and an energy window of 55-285 keV. When we used these optimal conditions for image acquisition, the estimation of 90Y activity in organs and tumors was within 15% of the true activities. CONCLUSIONS: The results of this study suggest that reasonable accuracy can be achieved in clinical radioimmunotherapy using 90Y-bremsstrahlung quantitation.

Beta Particles↗

Induction of micronuclei in peripheral blood lymphocytes of patients treated for rheumatoid or osteo-arthritis of the knee with dysprosium-165 hydroxide macroaggregates or yttrium-90 silicate.

The advantages of radiation synovectomy, using preparations containing dysprosium-165 (Dy-165), over conventional materials based on yttrium-90 (Y-90) include a more ideal spectrum of decay energies, and a much shorter half-life permitting quicker and more efficient treatment. A new therapeutic agent, Dy-165 hydroxide macroaggregates, has been developed for the treatment of arthritis making use of these advantages. As part of a clinical trial of this material 42 patients were examined for micronucleus frequency in their peripheral blood lymphocytes prior to, and 2 weeks after, radiation synovectomy using Dy-165 hydroxide macroaggregates or Y-90 silicate. In the majority of patients from each treatment group no significant increase in micronucleus frequency was observed. This indicates that in these cases leakage of material from the site of treatment was not resulting in detectable irradiation of circulating cells irrespective of the choice of radiopharmaceutical. The maximum increase in micronucleus frequency observed corresponded to a radiation dose to circulating cells of approximately 0.3 Gray.

Adult↗

Radioimmunotherapy of relapsed B-cell lymphoma with yttrium 90 anti-idiotype monoclonal antibodies.

Tumor-specific anti-idiotype (anti-Id) monoclonal antibodies (MoAbs) to B-cell lymphomas have been administered to patients, resulting in significant clinical responses. However, clinical responses have been limited by the emergence of Id-negative lymphoma. To overcome the problem of tumor heterogeneity, we conducted a pilot evaluation of the safety and effectiveness of yttrium 90 (90Y)-labeled anti-Id and shared Id (sId) MoAbs in non-Hodgkin's B-cell lymphoma. Nine patients with relapsed B-cell lymphoma in whom tumor was successfully targeted with 111In-labeled anti-Id MoAb were treated with 90Y-labeled anti-Id MoAb. A total of 19 courses (one to four per patient) were administered using 1,000 to 2,320 mg unlabeled clearing MoAb and 10 to 54 mCi 90Y MoAb per patient. Two of nine patients had a complete response, one a partial response, three stable disease, and three disease progression. Time to progression varied from 1 to 12 months. Toxicities were predominately hematologic, and only one patient developed infection and required transfusion. At progression, three of five assessable patients had Id-positive lymphoma and two had Id-negative lymphoma. Human antimouse antibodies (HAMA) did not develop in the patients after treatment. 90Y anti-Id MoAbs demonstrated excellent in vivo stability, produced significantly tumor regression in three of nine patients, exhibited acceptable toxicities, and elicited no HAMA formation. Further investigation of repetitive, low-dose 90Y anti-Id and MoAb therapy is warranted; however, the advantages of a pan B MoAb may prove the latter to be the agent of choice for the radio immunotherapy of B-cell lymphoma.

Adult↗

[Experimental study of internal radiation with yttrium-90 microspheres in the treatment of mouse transplanted hepatoma].

The effect of yttrium-90 microspheres in the treatment of mouse transplanted hepatoma H22 was studied. Seventy BALB/C mice with hepatoma H22 were randomly divided into 7 groups (A, B, C, D, E, F, G) and treated respectively with 37, 18.5, 14.8, 11.1, 7.4, 3.7 and 0 MBq/cm3 internal radiation by intratumoral injection of Y-90 microspheres. Dose-dependent therapeutic effects were observed. In group A and B, the tumor growth was markedly retarded and eventually un-palpable. Histological examinations showed complete necrosis of the tumor. In groups C,D, E,F, the tumor growth was also inhibited. However, patchy necrosis could be seen amid apparently normal tumor cells. Only isolated, spotty foci of necrosis were present in the untreated control tumors. The results indicate that a tumor of 1 cm diameter can be effectively treated by internal radiation with 18.5MBq Y-90 microspheres injected into the tumor.

Animals↗

Intraperitoneal indium-111- and yttrium-90-labeled human IgM (AC6C3-2B12) in nude mice bearing peritoneal carcinomatosis.

UNLABELLED: Radiolabeled monoclonal antibodies are utilized increasingly for the diagnosis and treatment of human cancer. Tumor targeting of radiolabeled human monoclonal IgM improves with compartmental administration and might be useful for the diagnosis or treatment of peritoneal carcinomatosis. METHODS: A human monoclonal antibody IgM lambda (AC6C3-B12) reactive with human adenocarcinomas was conjugated to isothiocyanato-2-benzyl-3-methyl-diethylenetriamine-penta-a cetic acid and labeled with either 111In or 90Y. Nude mice bearing intra-abdominal lumps of a human colorectal carcinoma cell line (SW620) were used as a model for peritoneal carcinomatosis. A human monoclonal antibody IgM lambda (CR4E8) reactive with human squamous-cell carcinoma was used as a control. RESULTS: Indium-111-IgM and 90Y-IgM immunoconjugates were compared in nude mice at 2, 24, 72, 120 and 144 hr after intraperitoneal administration. Both showed high specific tumor uptake. The tumor-effective half-lives of the immunoconjugates were 39 hr for indium and 46 hr for yttrium. Tumor-to-normal organ ratios were high and similar for both reagents. Only the femur uptake at later time points was relatively higher for the 90Y-IgM than for 111In-IgM. The tumor uptake of specific AC6C3-2B12 was about fourfold higher than the uptake of aspecific CR4E8 at 24 and 120 hr. CONCLUSION: The combination of 111In- and 90Y-labeled AC6C3-2B12 offers a new opportunity to develop safer and more effective methods for diagnosing and treating human patients with peritoneal carcinomatosis.

Animals↗

Renal cell carcinoma detection and systemic therapy with tumour-affine gallium-67 and with yttrium-90 citrate solutions.

BACKGROUND: There have been no major advances in the systemic detection of renal cell carcinoma (RCC) and its unpredictable metastases. Surgery, thus, remains the mainstay of the curative treatment for the localized disease. The propose of the present study has been to systemically detect and treat advanced RCC respectively with Ga-67 and Y-90 radiopharmaceuticals containing tumour-affine species. PATIENTS AND METHODS: Thirty-three RCC patients were imaged with Tc-99m-MDP and then with Ga-67 citrate solution in order to detect RCC and its metastases. Yttrium-90 citrate solution, containing the radionuclide species chromatographically and electrophoretically identical to those in RCC-affine Ga-67 solution, was administered i.v. for systemic therapy of advanced RCC. Total-body distribution of Y-90 was studied with a gamma-camera equipped with an ultra-high-sensitivity collimator. The efficacy of the therapy was studied by the clinical condition of the patient and by the total-body scintigraphic imaging with Tc-99m-MDP and with Ga-67 citrate solution. RESULTS: Ga-67 detects RCC bone metastases better than Tc-99m-MDP. Systemic therapy of RCC metastasized to bones, lung and brain was obtained with RCC-affine Y-90 citrate solution. CONCLUSIONS: Third group metal radionuclides, Ga-67 and Y-90, detect and treat advanced RCC.

Adult↗

Yttrium-90/indium-111-DOTA-peptide-chimeric L6: pharmacokinetics, dosimetry and initial results in patients with incurable breast cancer.

BACKGROUND: Radioimmunotherapy (RIT) using 131I-Chimeric L6 (ChL6) antibody has shown therapeutic promise for patients with breast cancer. To enhance this potential, a novel immunoconjugate was developed that targets adenocarcinomas like breast cancer and tightly binds yttrium-90 (90Y) for therapy and indium-111 (111In) for imaging. The radioimmunoconjugate consists of a macrocyclic chelator (DOTA) linked to ChL6 by a catabolizable peptide. 90Y-DOTA-peptide-ChL6 was designed to minimize the radiation dose to critical normal tissues, thereby improving the therapeutic index. MATERIALS AND METHODS: Three patients with incurable metastatic breast cancer received 90Y/111In-DOTA-peptide-ChL6 for 5 pharmacokinetics/dosimetry studies and one of these patients also received 2 therapy doses. Quantitative imaging of 111In and in vitro assay of 90Y and 111In in blood urine and bone marrow samples were obtained. RESULTS: 90Y/111In-DOTA-peptide-ChL6 was prepared at high purity and was stable in vivo. Assays of bone marrow revealed no evidence for escape of 90Y or 111In from the chelate. 111In imaging of tumors was excellent, providing a therapeutic index for tumor to marrow radiation as high as 229 to 1. 90Y and 111In provided comparable pharmacokinetics, as did tracer and therapeutic doses of radioimmunoconjugates. One patients that received 2 therapeutic doses of 90Y-DOTA-peptide-ChL6 showed regression of tumors and tumor markers. Toxicities were relatively minor and no anti-globulin response developed despite 5 immunoconjugate infusions. CONCLUSIONS: This first study in patients of radioimmunoconjugates with a catabolizable linker between the metal chelator and the antibody confirmed that these novel 90Y/111In-DOTA-peptide-ChL6 radioimmunoconjugates have significant potential. Tracer doses of 111In-DOTA-peptide-ChL6 for imaging predicted the behavior of therapeutic doses of 90Y-DOTA-peptide-ChL6. The latter radioimmunoconjugate induced regression of tumors and tumor markers without significant toxicity. When compared to earlier 131I-ChL6 dosimetry, 90Y-DOTA-peptide-ChL6 provided a therapeutic index several times better.

Antibodies, Monoclonal↗

Neodymium:yttrium-aluminum-garnet laser treatment of cystic granula iridica in horses: eight cases (1988-1996).

OBJECTIVE: To determine clinical features of cystic granula iridica in horses and outcome of horses treated with an ophthalmic neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. DESIGN: Retrospective study. ANIMALS: 8 horses. PROCEDURE: An ophthalmic Nd:YAG laser was used to deflate cysts in all horses. RESULTS: Horses were examined because of visual impairment (n = 5), decreased jumping performance (2), or head shaking (1). Clinical signs associated with cysts resolved in all horses after treatment. Short- and long-term complications did not develop, and cysts did not recur. CLINICAL IMPLICATIONS: Cystic granula iridica may cause vision impairment in horses. Treatment with an ophthalmic Nd:YAG laser appears to be safe and effective.

Aluminum↗

Indium-111- and yttrium-90-labeled human monoclonal immunoglobulin M targeting of human ovarian cancer in mice.

UNLABELLED: Most patients with ovarian cancer have disease in the peritoneal cavity. Treatment of this region is inadequate because recurrences are frequent. Increased radiation doses to tumor and, hence, greater tumor control may be possible with intraperitoneal (i.p.) administration of radiolabeled human monoclonal immunoglobulin M (IgM), which is reactive with tumor-associated antigens. METHODS: Biodistribution studies were performed in nude mice bearing i.p. nodules of human ovarian cancer after administration of human monoclonal IgMlambda (AC6C3-2B12), labeled with 111In or 90Y. Irrelevant 111In-labeled human IgMlambda (CH-1B9) and 90Y-aggregate served as specificity controls. RESULTS: Intravenous administration of 111In-labeled AC6C3-2B12 produced low tumor and high liver and spleen uptake. Intraperitoneal administration of AC6C3-2B12 labeled with 111In or 90Y resulted in rapid, high tumor uptake (>45% of injected dose per gram of tumor at 3 hr) that was at least three-fold higher than any normal organ. Biodistribution results were similar for 111In- and 90Y-labeled IgM. Tumor uptake of 111In-labeled AC6C3-2B12 was two-fold greater than that of 111In-labeled CH-1B9. Normal organ uptakes were similar for tumor-reactive and irrelevant IgM. Radioimmunoconjugates were retained in the peritoneal cavity for a prolonged period of time. Yttrium-90 aggregate demonstrated high tumor and bone uptake. CONCLUSION: Higher tumor uptake was observed after i.p. administration of tumor-reactive IgM than after irrelevant IgM. The in vivo behavior of tumor-reactive IgM was similar when it was radiolabeled with either 111In or 90Y. Therefore, 111In-based imaging studies can be used to predict the biodistribution of subsequently administered 90Y-labeled IgM. Further development of radiolabeled AC6C3-2B12 as a diagnostic and therapeutic agent for patients with advanced ovarian carcinoma is warranted.

Animals↗

Treatment of experimental choroidal melanoma with an Nd:yttrium-lanthanum-fluoride laser at 1047 nm.

OBJECTIVE: To evaluate the effect of a new infrared laser in the destruction of pigmented choroidal melanomas. METHODS: B16F10 melanomas were implanted in the subchoroidal space of 64 rabbits (tumor height, 2.0-4.0 mm). Laser radiation from an Nd:yttrium-lanthanum-fluoride laser (1047 nm) was delivered as a focused (beam waist, 25 micro m; irradiance, 100 kW/cm( 2)) raster-scanned transpupillary beam. To investigate melanin heating, treatment with focused light was compared with collimated light (beam waist, 2 mm; irradiance, 16 W/cm(2)). Fine-wire thermocouples were implanted at the base of 3 tumors for in vivo temperature measurements. Untreated animals were used as controls. RESULTS: Of 64 animals, 27 received a single treatment with focused 1047-nm light. The rate of complete tumor eradication was 91% (10 of 11 animals) at a dosage of 125 J/cm(2) and 75% (9/12) at 63 J/cm(2) to 87 J/cm(2). The eradication rate dropped to 25% (1 of 4) at 38 J/cm(2) or less (P<.001). Continuous tumor growth was observed in all animals treated with collimated radiation and in untreated controls. Temperature measurements indicated that tissue heating at the tumor base was more rapid at 1047 nm than at 805 nm. CONCLUSIONS: These data suggest that a single treatment with a focused, raster-scanned beam at 1047 nm may play a role in the destruction of pigmented choroidal melanoma. Focused irradiation at 1047 nm may provide more effective submillisecond heating of melanin than collimated irradiation, resulting in immediate photothermal disruption of tumor cells.

Animals↗

Myopic intrastromal photorefractive keratectomy with the neodymium-yttrium lithium fluoride picosecond laser in the cat cornea.

OBJECTIVE: To evaluate the refractive effects of myopic intrastromal photorefractive keratectomy (IPRK) with the neodymium-yttrium lithium fluoride (Nd-YLF) picosecond laser. METHODS: A 1053-nm Nd-YLF picosecond laser was used to produce myopic IPRK in cat corneas at threshold energy densities. Preoperative corneal topography and ultrasonic pachymetry were performed followed by IPRK in one eye each of 21 cats. No anti-inflammatory medications were administered. Postoperative corneal topography, ultrasonic pachymetry, and slit-lamp examination were performed at scheduled intervals. RESULTS: An average topographic flattening of 11.4 diopters and pachymetric thinning of 50 microns at the center of the treatment zone were observed by 6 weeks following treatment. The average diameter of the zone of flattening was 5.1 mm at 6 weeks and 6.0 mm at 12 weeks postoperatively. At 6 months postoperatively, the average central corneal power was unchanged, while the average central thickness had returned to the preoperative value. A mild subepithelial haze was detected at 1 month following IPRK, which was barely perceptible at the second through sixth months. Regression of the topographic effects of PRK was not observed. CONCLUSION: Intrastromal PRK with the Nd-YLF picosecond laser produces central flattening of the cat cornea with barely perceptible stromal haze and no regression of topographic effect after 6 months in the absence of treatment with anti-inflammatory agents.

Animals↗

In vivo trial comparing patients' tolerance of Q-switched Alexandrite (QS Alex) and Q-switched neodymium:yttrium-aluminum-garnet (QS Nd:YAG) lasers in the treatment of nevus of Ota.

BACKGROUND AND OBJECTIVES: Different types of Q-switched lasers have been found to be effective in the treatment of nevus of Ota. However, a clinical trial involving in vivo comparison of the use of different laser systems has not been performed. The aim of the present study was to compare the patient tolerance of Q-switched Alexandrite (QS Alex) and Q-switched neodymium:yttrium-aluminum-garnet (QS Nd:YAG) lasers in the treatment of nevus of Ota. STUDY DESIGN/MATERIALS AND METHODS: Thirty-three patients (11 male, 22 female) were recruited for this study, and 45 treatment sessions were performed. Half of each lesion was treated with QS Alex and the other half with QS Nd:YAG laser. Patients were interviewed with a visual analog scale questionnaire immediately after treatment and 1 week later. Questions included the degree of pain, swelling, and bleeding. RESULTS: The immediate pain after treatment was more severe for QS Alex than for QS Nd:YAG laser. However, 1 week after laser therapy, most patients found QS Alex to be superior. CONCLUSION: Patients tolerate QS-Alex better than QS Nd:YAG. This finding is important because patients with nevus of Ota are often children, and multiple laser sessions are necessary for complete resolution of the lesion.

Activities of Daily Living↗

Endobronchial radiation therapy with or without neodymium yttrium aluminum garnet laser resection for managing malignant airway obstruction.

BACKGROUND: Previous reports have shown low-dose-rate (LDR) afterloading Ir-192 endobronchial radiation therapy (EnBRT) to effectively palliate symptoms in patients with malignant airway obstruction. The authors retrospectively assessed the consequences of LDR EnBRT with or without neodymium yttrium aluminum garnet (Nd:YAG) laser resection in 37 patients. METHODS: Between February 1986 and June 1991, 37 patients with malignant airway obstruction were treated with LDR EnBRT at The Cleveland Clinic Foundation. Inclusion criteria for LDR EnBRT with or without Nd:YAG laser resection were patients with recurrent, symptomatic endobronchial lesions treated previously with external beam irradiation. Of the 37 patients, 21 patients with endobronchial lesions underwent Nd:YAG laser resection; 16 patients with mainly extrinsic lesions received EnBRT only. Before EnBRT, selected patients (7 of 16 in the nonlaser-treatment group and 14 of 21 in the laser-treatment group) received additional external beam treatments of 2000 cGy/10 fractions. The LDR afterloading Ir-192 technique was used to deliver approximately 30 Gy to a 1.0-cm radius target. RESULTS: All patients had one or more of the following symptoms: 1) dyspnea, 2) fever, 3) cough, and 4) hemoptysis. Good-to-excellent symptom relief was apparent in 16 of 21 (76.2%) laser-treated patients and in 12 of 16 (75%) nonlaser-treated patients. Follow-up bronchoscopy in 28 patients revealed tumor regression in 22 (79%). Median survival time was 16.3 weeks in the laser group and 11.7 weeks in the nonlaser group (P = 0.36). Longer median survival times were noted in laser-treated (22.8 weeks) and nonlaser-treated (16.4 weeks) patients receiving additional external beam treatments. Exsanguination occurred in 7 of 21 (33.3%) laser-treated patients and in 4 of 16 (25%) nonlaser-treated patients. The only factor affecting the exsanguination rate was implant location: 6 of 11 (54.5%) patients had lesions in the right or left upper lobe. CONCLUSIONS: EnBRT alone or with Nd:YAG laser resection provided good-to-excellent symptom palliation in these patients although a high rate of exsanguination occurred in both groups.

Adult↗

Geometrical structure of yttrium and metal-bromine complexes in solution: limitations of extended X-ray absorption fine structure analysis (EXAFS).

An extensive study on the appearance of multi-electron features in the X-ray absorption spectra of several yttrium(III)-based compounds has been performed. The existence of a multi-electron transition of non-negligible intensity within the extended X-ray absorption fine structure (EXAFS) region of the Y K-edge spectra has been proven. The impact of such features in the EXAFS analysis is made evident for aqueous solutions of YBr3 x 6H2O in liquid and glassy states in the concentration range 0.005-2.0 M, in which this transition induces an overestimation in the coordination numbers derived from EXAFS. We have performed theoretical computation of cross-sections for the double-electron processes at the K-edge of both Y and Br. These computations have been applied to the experimental EXAFS K-edge spectra of both Y and Br in several solids and in aqueous solutions. While in the case of Y K-edge spectra the presence of such multi-electron transitions was seen to seriously affect the standard EXAFS analysis, its influence in the case of Br K-edge spectra was determined to be negligible.

Journal Article↗

Poor palliation of colorectal malignancy with the neodymium yttrium-aluminium-garnet laser.

The neodymium yttrium-aluminium-garnet (NdYAG) laser was used to palliate the symptoms of 38 patients with rectal carcinoma unsuitable for radical surgery. All patients with small tumours (n = 6) reported resolution of their symptoms. In contrast, those with large tumours frequently showed little improvement (n = 18) and alternative surgical management was necessary in 12 patients. The overall early mortality rate (less than 1 month after first treatment) was 21 per cent. The NdYAG laser offers good palliation and may even cure small colorectal tumours in patients who are unsuitable for surgery. For large circumferential tumours, those associated with obstruction and those close to or involving the anal sphincters, however, the results are poor and better symptom control may be achieved by other means.

Aged↗

Yttrium and lanthanide complexes with various P,N ligands in the coordination sphere: synthesis, structure, and polymerization studies.

Yttrium and lanthanide complexes with different P,N ligands in the coordination sphere have been synthesized. First the chloride complexes [{CH(PPh2NSiMe3)2}Ln{(Ph2P)2N}Cl] (Ln = Y (1 a), La (1 b), Nd (1 c), Yb (1 d)) having the bulky [CH(PPh2NSiMe3)2]- and the flexible [(Ph2P)2N]- ligands in the same molecule were prepared by three different synthetic pathways. Compounds 1 a-d can be obtained by reaction of [{[CH(PPh2NSiMe3)2]LnCl2}2] with [K(thf)nN(PPh2)2] (n = 1.25, 1.5) or by treatment of [{(Ph2P)2N}LnCl2(thf)3] with K[CH(PPh2NSiMe3)2]. Furthermore, a one-pot reaction of K[CH(PPh2NSiMe3)2] with LnCl3 and [K(thf)nN(PPh2)2] leads to the same products. Single-crystal X-ray structures of 1 a-d show that the conformation of the six-membered metallacycle (N1-P1-C1-P2-N2-Ln) which is formed by chelation of the [CH(PPh2NSiMe3)2]- ligand to the lanthanide atom is influenced by the ionic radius of the central metal atom. In solution dynamic behavior of the [(Ph2P)2N]- ligand is observed, which is caused by rapid exchange of the two different phosphorus atoms. Further reaction of 1 b with KNPh2 resulted in [{(Me3SiNPPh2)2CH}La{N(PPh2)2}(NPh2)] (2). Compounds 1 a-d and 2 are active in the ring-opening polymerization of epsilon-caprolactone and the polymerization of methyl methacrylate. In some cases high molecular weight polymers with good conversions and narrow polydispersities were obtained. In both polymerizations the catalytic activity depends on the ionic radius of the metal center.

Journal Article↗

Highly hydrated cations: deficiency, mobility, and coordination of water in crystalline nonahydrated scandium(III), yttrium(III), and lanthanoid(III) trifluoromethanesulfonates.

Trivalent lanthanide-like metal ions coordinate nine water oxygen atoms, which form a tricapped trigonal prism in a large number of crystalline hydrates. Water deficiency, randomly distributed over the capping positions, was found for the smallest metal ions in the isomorphous nonahydrated trifluoromethanesulfonates, [M(H2O)n](CF3SO3)3, in which M = Sc(III), Lu(III), Yb(III), Tm(III) or Er(III). The hydration number n increases (n = 8.0(1), 8.4(1), 8.7(1), 8.8(1) and 8.96(5), respectively) with increasing ionic size. Deuterium (2H) solid-state NMR spectroscopy revealed fast positional exchange between the coordinated capping and prism water molecules; this exchange started at temperatures higher than about 280 K for lutetium(III) and below 268 K for scandium(III). Similar positional exchange for the fully nonahydrated yttrium(III) and lanthanum(III) compounds started at higher temperatures, over about 330 and 360 K, respectively. An exchange mechanism is proposed that can exchange equatorial and capping water molecules within the restrictions of the crystal lattice, even for fully hydrated lanthanoid(III) ions. Phase transitions occurred for all the water-deficient compounds at approximately 185 K. The hydrated scandium(III) trifluoromethanesulfonate transforms reversibly (DeltaH degrees = -0.80(1) kJ mol(-1) on cooling) to a trigonal unit cell that is almost nine times larger, with the scandium ion surrounded by seven fully occupied and two partly occupied oxygen atom positions in a distorted capped trigonal prism. The hydrogen bonding to the trifluoromethanesulfonate anions stabilises the trigonal prism of water ligands, even for the crowded hydration sphere of the smallest metal ions in the series. Implications for the Lewis acid catalytic activity of the hydrated scandium(III) and lanthanoid(III) trifluoromethanesulfonates for organic syntheses performed in aqueous media are discussed.

Journal Article↗

Three-year recurrence-free survival in a patient with recurrent medulloblastoma after resection, high-dose chemotherapy, and intrathecal Yttrium-90-labeled DOTA0-D-Phe1-Tyr3-octreotide radiopeptide brachytherapy.

BACKGROUND: Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, beta-emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2-expressing tumor remnants, which persisted despite conventional and high-dose chemotherapy and intercurrent resection of the lesion. METHODS: A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high-dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium-111-DOTATOC test injection indicated sst2-expressing tumor remnants within the cauda equina. Consequently, 4 cycles of [90Y]-DOTATOC (4x562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. RESULTS: The consolidating intrathecal brachytherapy using [90Y]-DOTATOC was tolerated well. A complete remission was achieved for a 3-year period. The only remaining deficit was urinary incontinence. CONCLUSIONS: Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high-dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further.

Antineoplastic Agents↗