Respiratory system deposition with a novel aerosol delivery system in spontaneously breathing healthy adults.

BACKGROUND: Intravenous magnesium sulfate (MgSO(4)) in children and adults with refractory acute asthma is effective, but therapy may be limited by systemic hypotension that might be avoided with the aerosol route. Inhaled MgSO(4) has a relatively high dose (volume) requirement. This, plus the use of inefficient delivery systems, may explain the lack of efficacy of inhaled MgSO(4) in some studies. An in vitro study suggested that the AeroNeb Go with the Idehaler Pocket and a face mask would deliver 16 mg/min of MgSO(4) to the respiratory system in older children, and approximately a fifth for toddlers, but no in vivo data exist. METHODS: Saline mixed with a radiolabel was used as a proxy for the 100 mg/mL MgSO(4) solution. In 5 adult males the rate of deposition was measured using nuclear medicine techniques. The radiolabel deposition below the vocal cords was converted to the rate of deposition of MgSO(4) and compared to the results from an in vitro model using adult respiratory patterns. RESULTS: The mean ± SD rate of deposition was 12.6 ± 1.9 mg/min. The reasons for this lower deposition, compared to the in vitro estimate, was most likely the exhalation of anatomical dead space aerosol, which would have been captured on the inspiratory filter in vitro. CONCLUSIONS: These in vivo data confirm the deposition data predicted in the in vitro study, although caution should be used in extrapolating the results to children. This device appears suitable for the clinical trial of inhaled MgSO(4) in children and adults with refractory asthma.

Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma.

PURPOSE: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of (131)I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after (131)I-MIBG treatment. PATIENTS AND METHODS: Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg (131)I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. RESULTS: Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 x 10(3)/microL). Patients reached platelet nadir earlier than neutrophil nadir (P <.0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to (131)I-MIBG therapy (P

Pinhole imaging of 131I-metaiodobenzylguanidine (131I-MIBG) in an animal model of neuroblastoma.

PURPOSE: To evaluate (131)I-MIBG scintigraphic localization of xenotransplanted and spontaneously arising neuroblastomas in murine models of high-risk neuroblastoma. METHODS: Neuroblastoma xenografts were created by inoculation of human neuroblastoma cell suspensions into the subcutaneous flanks of athymic nude mice. In addition, spontaneous paraspinal neuroblastomas were detected by direct palpation in MYCN transgenic mice. After measured tumor volumes exceeded 200 mm(3), each mouse received an intraperitoneal injection of 18 muCi/g (131)I-metaiodobenzylguanidine ((131)I-MIBG). Pinhole scintigraphy was performed to evaluate the MIBG biodistribution and to attempt to visualize the tumors. Each mouse was imaged on a gamma camera equipped with a 3-mm pinhole on one head and an HEGP collimator on the other. RESULTS: Images demonstrated absorption of radiolabeled MIBG and visualization of tumors. Analysis of the images allowed for quantification of relative MIBG uptake and for determination of linear and area measurements of the tumors. CONCLUSION: High-energy pinhole imaging effectively demonstrates uptake of radiolabeled MIBG by human neuroblastoma tumors in murine laboratory models. This technique allows for in vivo assessment of tumor burden. In the future, we plan to use this method to evaluate sensitivity for detecting metastatic spread as well as investigating the therapeutic efficacy of high-dose (131)I-MIBG in combination with radiosensitizing agents.