Positron emission tomography (PET) studies have indicated that alteration of active transport contributes to increased net amino acid accumulation into human brain tumors. We compared the uptake of 11C-methionine (MET) and the K+ analog 82Rubidium (RUB) in 30 patients suffering from various brain tumors using PET. MET and RUB accumulated rapidly in tumor tissue and remained on average at a stable level thereafter from which normalized uptake values calculated (tissue radioactivity over injected radioactivity x body weight (NU). K1 (RUB) and K1, k2, k3 (MET) were also estimated using non-linear rate constant fitting in 17/30 patients. NU and K1 values for MET and RUB were higher in meningiomas compared to gliomas and were significantly correlated for the whole spectrum of tumors (p < 0.0001). When meningiomas were excluded, the correlation was maintained. K3 values for MET (metabolic rate) in tumors were in the range of normal brain. No correlation between RUB and MET was found for normal brain. with increasing rub intake the ratio of Nu MET over Nu RUB approached the value of 1.0. These results suggest that apart from active transport, also passive diffusion across the blood-brain barrier (BBB) may account for MET uptake from blood into tumor tissue. This probably limits the use of MET in the differential diagnosis of brain lesions where BBB disruption is present.
Volunteers were given a steady intake of various individually different daily dosages of ascorbic acid. After 3 weeks 1-14C-labelled ascorbate was given together with various amounts of unlabelled ascorbic acid (90-1000 mg). Regardless of the total daily dose in cases where the carrier dose amounted to 180 mg or more, carbon dioxide was recovered from the breath. The amount recovered ranged from 1 to more than 30% of the given dose. The larger the amount of carrier the larger was the amount of label recovered as carbon dioxide. It is suggested that the formation of carbon dioxide is due to a presystemic effect as a result of microbiological or chemical degradation of ascorbate in the intestine.
There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.
A key limitation in developing radiotherapeutic proteins is the expense of manufacturing the drug in small batches using traditional reaction vessels. Removing limitations on the quantity of protein labeled at any one time significantly decreases the cost of production, and nowhere is the need for cost-effective radiotherapeutics more acute than in the treatment of cancer. Methods: We describe a novel method that can rapidly radiolabel, theoretically, unlimited amounts of protein, without causing significant damage to binding potency or structural integrity. Our process controls the reaction rate for the isotope and reactants as they simultaneously flow through a reaction tube. Results: We have demonstrated proof of principle by labeling nearly a gram of antibody with 481 GBq (13 Ci) of 131 I during a single 30-min reaction run. Conclusion: Simple to construct, our system is already used to manufacture a radiolabeled antibody, both in the United States and in India, as part of clinical trials to treat glioblastoma multiforme. Modified, this system may be also applicable for nonradioactive labeling.
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