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Objectives: Intra-articular injection of 169Erbium-citrate (169Er-citrate; radiosynoviorthesis or radiosynovectomy) is an effective local treatment of rheumatic joint diseases. However, its efficacy in corticosteroid-resistant rheumatoid arthritis-affected joints has not been clearly demonstrated., Methods: A double-blind, randomised, placebo-controlled, international multicentre study was conducted in patients with rheumatoid arthritis with recent (< or = 24 months) ineffective corticosteroid injection(s) into their finger joint(s). Eighty-five finger joints of 44 patients were randomised to receive a single injection of placebo (NaCl 0.9%) or 169Er-citrate. Results of evaluation 6 months later were available for 82 joints (46 metacarpophalangeal and 36 proximal interphalangeal joints) of 42 patients: 39 169Er-citrate-injected joints and 43 placebo-injected joints. Efficacy was assessed using a rating scale for joint pain, swelling and mobility., Results: Intent-to-treat analysis of the results of the 82 joints showed a significant effect of 169Er-citrate compared to placebo for the principal criteria decreased pain or swelling (95 vs 79%; p = 0.038) and decreased pain and swelling (79 vs 47%; p = 0.0024) and for the secondary criteria decreased pain (92 vs 72%; p = 0.017), decreased swelling (82 vs 53%; p = 0.0065) and increased mobility (64 vs 42%; p = 0.036). Per-protocol analysis, excluding 18 joints of patients who markedly changed their usual systemic treatment for arthritis, gave similar percentages of improvement but statistical significance was lower owing the reduced power of the statistical tests., Conclusion: These results confirm the clinical efficacy of 169Er-citrate synoviorthesis of rheumatoid arthritis-diseased finger joints after recent failure of intra-articular corticotherapy.

Objective: The aim of this international multicentric randomized phase 3 clinical trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186-sulfide (186Re) to intra-articular corticotherapy in patients with clinically controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized joints remained painful or swollen., Methods: One hundred and twenty-nine joints in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)] were randomized to receive intra-articular injections of either 186Re-sulfide (64 +/- 4 MBq), or cortivazol (Altim) 3.75 mg. Clinical assessment was performed before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS for joint swelling and mobility and a 2-step VRS for the radiological stage. The Mantel-Haenszel test was used for qualitative variables, analysis of variance (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse analysis., Results: 186Re was observed to be statistically superior to cortivazol at 18 and 24 months while no statistical difference was seen for any criterion at 3, 6 and 12 months post injection. At 24 months, the difference in favor of 186Re was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p = 0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p = 0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of relapse in corticoid treated joints, but only from the second year of follow-up. No serious side effect was observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used., Conclusion: 186Re-sulfide and cortivazol had similar efficacy up to 12 months post-injection, but 186Re became clearly more effective at 18 and 24 months, for all criteria monitored and for RA outcome. Therefore, 186Re RSO can be recommended for routine clinical use.

Unlabelled: The somatostatin analog 111In-pentetreotide was evaluated in 11 children with sympathetic embryonic cell-derived tumors., Methods: Six neuroblastomas, four ganglioneuroblastomas and one ganglioneuroma (benign) were imaged 4 and 24 hr after injection of 111In-pentetreotide (5 MBq/kg) and 24 hr after administration of 123I-metaiodobenzylguanidine (MIBG) (3.7 MBq/kg)., Results: Primary tumor was detected with both tracers in four of the five patients studied before surgery (one Stage III neuroblastoma, one Stage IV neuroblastoma, one Stage IVs neuroblastoma, one ganglioneuroblastoma), but the ganglioneuroma was not localized. Detection of bone marrow metastases was clearly better with 111In-pentetreotide in two patients, similar or slightly better with MIBG in six and (true) negative with both procedures in three. The positivity rate of 111In-pentetreotide for imaging of metastases was higher in undifferentiated malignant tumors (six neuroblastomas: two very positive, three positive, one true-negative) than in histologically well-differentiated tumors (four ganglioneuroblastomas: three weakly positive, one true-negative). All patients with positive 111In-pentetreotide imaging results had elevated urinary catecholamine levels, and the two most 111In-pentetreotide-positive metastases were found in neuroblastomas from children with an aneuploid primary tumor. The 111In-pentetreotide and MIBG results were only partly correlated with bone marrow status, as assessed by immunocytological and histological studies at the time of scanning., Conclusion: Abnormalities detected in 111In-pentetreotide uptake were slightly different from those seen with MIBG as a first-line routine method in neuroblast-derived tumors. However, some MIBG as a first-line routine method in neuroblast-derived tumors. However, some MIBG-negative tumor sites were detected by 111In-pentetreotide in patients with neuroblastomas. Thus, 111In-pentetreotide could provide novel information on the biology and prognosis of tumors whose clinical significance remains to be defined.

A 33-year-old woman, who at 29 underwent mastectomy for a localised breast cancer (TINOMO), presented a relapse shown by a rapid rise in seric level of CEA. The classical complete work-up was negative. The location of the relapse was demonstrated by anti-CEA immunoscintigraphy. Radiotherapy, hormonotherapy and chemotherapy allowed to achieve a complete remission with normalization of CEA level and of immunoscintigraphy.

A cocktail of three monoclonal F(ab')2 fragments against three distinct epitopes of calcitonin or PDN 21 was labelled with either 111In or 131I. These F(ab')2 fragments, a control 125I-F(ab')2 fragment and 99mTc-pertechnetate were injected into four patients suffering from medullary thyroid carcinoma. Scintigraphy data were processed by energy factor analysis for an optimal separation of images corresponding to each isotope. The best tumor detection was obtained 1-3 days after injection of the 111In-F(ab')2 cocktail which clearly labeled the thyroid tumors in the four patients (smallest tumor detected, 0.6 cm) as well as lymph node and bone metastases. In the liver, positive detection was only successful with the 131I-labeled cocktail. These results were confirmed by counting rates of resected specimens which provided average specificity indices ranging from 3.3 to 13.1. Anticalcitonin antibodies could be particularly useful for immunoscintigraphy detection of residual or recurrent medullary thyroid carcinoma in patients with elevated calcitonin serum level.

The cytotoxicities of free cyanoacrylic nanoparticles, free Adriamycin, Adriamycin-loaded nanoparticles and a mixture of Adriamycin and nanoparticles are compared in cancer cell cultures. Increased cytotoxicity was observed in the sensitive (DC3F) subline when Adriamycin was in particulate form rather than free. In the derived pleiotropic resistant subline (DC3F AD/AZA), sensitivity to Adriamycin was completely restored with the conjugate. Addition of verapamil or amiodarone allowed an enhancement of efficiency of tenfold for free Adriamycin and between two- and fourfold for its conjugate form. Vectorization by nanoparticles and pharmacological modulation of cell membrane can act in synergy in synergy to overcome the resistance to Adriamycin in vitro.