123I-MSP and F[11C]MSP: new selective 5-HT2A receptor radiopharmaceuticals for in vivo studies of neuronal 5-HT2 serotonin receptors. Synthesis, in vitro binding study with unlabelled analogues and preliminary in vivo evaluation in mice.

In vitro binding study on bovine brain membranes using [3H]SCH23390, [3H]spiperone, [3H]prazosin and [3H]RP62203 as radioligands (for D1, D2, alpha1 and 5-HT2A receptors respectively) indicate that the new butyrophenones 8-[3-(4-fluorobenzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]de can-4-one (FMSP) and 8-[3-(4-iodobenzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]deca n-4-one (IMSP) exhibit a significantly higher selectivity for the 5-HT2A over D1, D2 and alpha1 receptors. Consequently, the radiolabelled analogues F[11C]MSP and 123I-MSP were prepared in attempt to obtain potential radiopharmaceuticals for in vivo imaging of neuronal 5-HT2A receptors with positron emission tomography (PET) and single photon emission tomography (SPET). F[11C]MSP was synthesized by reaction of [11C]CH3I with 8-[3-(4-fluorobenzoyl)propyl]-1,3,8-triazaspiro[4,5]decan-4- one (DMSP) in 12 +/- 3% radiochemical yield, whereas 123I-MSP was obtained in 82 +/- 8% radiochemical yield by a no-carrier-added Cu(I)-assisted [123I]iododebromination of 8-[3-(4-bromo-benzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]de can-4-ene (BrMSP). In vivo pharmacokinetic and brain binding characterization of 123I-MSP assessed in mice following intravenous injection, showed a fast clearance of 123I-MSP from blood and relatively high initial uptakes in the liver, kidneys and in the lung. Significant uptake and long retention were observed in the brain (up to 1.64% i.d., 60 min p.i.), with a regional accumulation of radioactivity consistent with the reported 5-HT2A receptors distribution in the brain. Frontal cortex to cerebellum ratio of 3.5 was calculated at 60 min p.i. Furthermore, the initial brain uptake was significantly reduced after pretreatment of the animals with ritanserin, a selective 5-HT2 antagonist, and by preinjection of the non-radiolabelled analog IMSP, thus indicating the specificity of the brain uptake. These data suggest that 123I-MSP may be a promising compound for studying the serotoninergic 5-HT2 receptors with SPET. Due to the low specific activity of F[11C]MSP currently obtained by the [11C]methylation reaction, systematic in vivo investigation of F[11C]MSP are as yet not feasable.

Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma.

UNLABELLED: The present investigation is an evaluation of intermediate and long-term side effects in patients after high-dose radioiodine treatment due to differentiated thyroid carcinoma. METHODS: A total of 203 patients were interviewed using a standardized questionnaire. RESULTS: After radioiodine treatment, 76.8% of the patients reported intermediate (from discharge up to 3 mo) or long-term (more than 3 mo after treatment) complaints, and 61.1% reported long-term side effects. Nonstochastic side effects included sialoadenitis, which occurred in 33.0% of cases, and 27.1% of patients suffered from a transient loss of taste or smell. More than 1 yr after the last radioiodine application, 42.9% of patients suffered from reduced salivary gland function. Complete xerostomia occurred in 4.4% of patients. Hematological abnormalities were found in 9 patients. In 28.1% of patients a transient episode of alopecia was reported. In 22.7% of patients chronic or recurrent conjunctivitis was reported, and 4 patients underwent dacryocystorhinostomy; 13.8% of patients suffered from an increased frequency of influenza, but 3.4% reported a reduced occurrence of such infections. For sialoadenitis, the loss of taste/smell and dry mouth, the dependence on accumulated activity was significant. CONCLUSION: Severe long-term side effects are rare after high-dose radioiodine treatment. Moderate side effects are common. The side effects are commonly the result of radiation damage to the salivary glands. The frequency of such complaints advocates regular protection of the salivary glands.

Diagnosis of osteomyelitis. Accuracy and limitations of antigranulocyte antibody imaging compared to three-phase bone scan.

Thirty-seven patients with suspected osteomyelitis in conjunction with diabetic gangrene (N = 14, group 1), arthroplasty (N = 8, group 2), and various diseases (N = 15, group 3) were examined. Three-phase bone scans, followed by granulocyte imaging using I-123 labeled anti-NCA 95 monoclonal antibodies, were performed to evaluate and compare the diagnostic accuracy of both procedures. Final diagnosis was established histologically, bacteriologically, or by both methods either through the clinical course or by long-term follow-up in patients in group 1. Osteomyelitis was proven in 17 out of the 37 patients. Bone and antigranulocyte imaging demonstrated positive results in all patients with osteomyelitis (sensitivity 100% for each method). No signs of skeletal infection were found in 20 patients. Fifteen of these patients had no antigranulocyte antibody accumulation, resulting in 75% specificity. Ten patients without infection had normal three-phase bone imaging results (specificity 50%). Antigranulocyte imaging results were negative in 6 out of 10 patients without osteomyelitis in groups 2 and 3 whose bone imaging results were questionable. However, because of identical bone and granulocyte imaging results, no increase of diagnostic accuracy could be obtained by additional granulocyte imaging in patients with diabetic gangrene. Final diagnoses of false-positive antigranulocyte studies were aseptic osteonecrosis (N = 2), loosening of prostheses, gouty arthritis, and pain after arthrolysis. In summary, antigranulocyte antibody imaging offered high sensitivity and acceptable specificity for the diagnosis of osteomyelitis. Diagnostic accuracy can be improved through the adjuvant use of antigranulocyte imaging for patients with suspected osteomyelitis, especially when radiographic and scintigraphic results are questionable or unreliable.

Functional results of radioiodine therapy with a 300-Gy absorbed dose in Graves' disease.

The aim of this study was to assess the results of high-dose radioiodine therapy given to 43 patients with recurrent hyperthyroidism due to Graves' disease between 1986 and 1992. We chose an intrathyroidal absorbed dose of 300 Gy and determined the applied activity individually, which ranged from 240 to 3120 MBq with a median of 752 MBq. Hyperthyroidism was eliminated in 86% of cases after 3 months and in 100% after 12 months. No patient required a second radioiodine treatment. The incidence of hypothyroidism was 63% after 3 months and 93% after 18 months. Neither the pretherapeutic thyroid-stimulating immunoglobulin level nor the degree of co-existing endocrine ophthalmopathy was correlated with the time at which hypothyroidism developed. Patients with previous radioiodine therapy developed hypothyroidism earlier than patients with previous thyroid surgery. The results show that ablative radioiodine therapy with a 300-Gy absorbed dose is a very effective treatment of hyperthyroidism in Graves' disease, but it should be restricted to patients with recurrent hyperthyroidism combined with severe co-existing disorders or episodes of unfavourable reactions to antithyroid drugs.

Effect of eicosapentaenoic acid in asthma.

The role of arachidonic acid metabolites in the pathogenesis of airway inflammation and clinical asthma is currently unknown. The addition of eicosapentaenoic acid (EPA) to the diet of humans has been shown to generate metabolites that are less potent than their arachidonic acid counterparts. The substitution of EPA for arachidonic acid metabolites in patients might cause a decrease in airway inflammation and an improvement in clinical asthma. We studied the effect of addition of EPA to the diet of twelve asthmatic patients. Standard clinical evaluations and pulmonary function tests were done on weeks 0, 3, 6, 10, 12 and 14. Patients ingested either low-dose EPA (0.1 g/day) or high-dose EPA (4.0 g/day) from weeks 6-14 (total of 8 weeks). There was no difference in clinical status or pulmonary function between groups at the start of the study. There was no change in clinical status or pulmonary function between or within groups at the end of 8 weeks of EPA ingestion.