For more than a year,124I (T=4.15 d) has been produced routinely with a compact cyclotron by irradiation of124TeO2 with 14 MeV deuterons, followed by dry distillation of the iodine radioisotopes formed from irradiated target materials. The following by-products have been measured and compiled in each charge: 13.2-d123I, 60-d125I, 13.0-d126I, 12.4-h130I and 8.02-d131I. The data show that after 45 h decay time, the sum of the activities of these nuclides is less than 5% of the124I activity. Observation of this limit has been required by the Swiss Regulatory Agencies for a PET study of cell proliferation in human brain tumors using [124I] IUdR.
-Methyltyrosine was iodinated in position 3 of the aromatic ring by means of an electrophilic iodination method using chloramine-T in a phosphate buffer solution. In a mixture containing -methyltyrosine, chloramine-T and a small amount of NaI as a carrier the reaction was complete within 15 min at room temperature. After purification by radio high pressure liquid chromatography /HPLC/ radiochemical yields of 77.6±3.2% were obtained. Radiochromatograms also revealed a small amount of an impurity, probably chlorinated 3-123I--methyltyrosine. After dissolving in isotonic phosphate buffer and sterile filtration the solution was ready for nuclear-medical applications.
Using a distillation method for the separation of18F-fluoride from aqueous18F-solutions obtained after cyclotron irradiation of a water target by means of the16O(3He, p)18F reaction, the radiohalogen could be generated as a highly reactive species for nucleophilic substitution reactions. Thus, with the starting compounds 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl--D-mannopyranose and 1,2:5,6-di-O-isopropylidene-3-O-trifluoromethanesulfonyl--D-allofuranose18F-2-deoxy-2-fluoro-D-glucose (2-18FDG) and18F-3-deoxy-3-fluoro-D-glucose (3-18FDG) could be synthesized with radiochemical yields of 71.6% and 85.9%, respectively. Including purification by HPLC, the total preparation time was 70 min, yielding the glucose derivatives in a no-carrier-added state. Specific activities coold be calculated to be greater than 103 Ci/mmol.
By comparison of three halogenated nicotinic acid derivatives, viz. 2–18F-, 6–18F-and 6–123I-nicotinic acid diethylamide (2–18F-NADA, 6–18F-NADA, 6–123I-NADA) the biodistribution of18F-and123I-radioactivity in mice was determined. For the two fluoro-compounds the results indicate nearly similar time-activity curves in almost all organs investigated, while the iodo-derivative exhibits significant differences: for the brain and the heart a complete elimination of123I-radioactivity takes place within 4 hours, time-activity curves of the liver and the kidneys show higher maximal accumulations compared to the fluorinated derivatives and activity in the stomach increases continously within a time period of 2 hours to a maximum which is about 5 times higher than that of 6–18F-NADA. For the lung drastic differences can also be observed in case of 6–123I-NADA which accumulates with a dose of about 40%/g already 30 seconds after injection and exceeds the corresponding values for 2–18F-NADA and 6–18F-NADA by a factor of about 6, followed by a biexponential decrease. De-fluorination reactions from the aromatic ring can be excluded, as could be shown by the low accumulation of18F-radioactivity in bones after application of 6–18F-NADA.
Authors:E. Knust, C. Müller-Platz, and M. Schüller
2-[18F]-nicotinic acid diethylamide was prepared by nucleophilic aromatic substitution in an acetamide melt of the corresponding
chloro-compound and purified by high pressure liquid chromatography. Optimization of the reaction conditions led to a maximum
radiochemical yield of about 50% within less than one half-life of18F. Tissue distribution of 2-[18F]-nicotinic acid diethylamide in various organs of mice showed a very fast accumulation of activity in the brain (mean body
concentration MBC-239%) with a brain to blood ratio of 1.34.
Authors:H. Machulla, E. Knust, K. Vyska, and M. Wolf
In hearts of mice the accumulation of 15-/para-123I-phenyl/-pentadecanoic acid /IPPA/ was determined 3 min after injection under different conditions. Using propionate as an agent competing with the albumin binding sites for fatty acids, the concentration of free fatty acids was increased in the circulating blood and the myocardial uptake of IPPA rose from 38.8±3.7% inj. dose/g under normal conditions to 46.2±5.1% inj. dose/g. On the other hand, the addition of 2-Br-palmitic acid reduced the myocardial uptake to a value of 31.0±2.5 inj. dose/g due to the known effect of blocking the transport of fatty acids into the cells. The results suggest the existence of a carrier-mediated transport process of fatty acids into the myocardial tissue.
Authors:E. Knust, H. Machulla, P. Zabel, Chr Astfalk, and U. Schmidt
By nucleophilic isotope exchange, 6-123I-nicotinic acid diethylamide (6-123I-NADA) was synthesized in a solution of the starting compound and catalytic amounts of CuCl in acetic acid. After purification by high pressure liquid chromatography radiochemical yields up to 97% could be obtained within 10 minutes. In mice the radioactivity was rapidly accumulated in the brain reaching the maximum (4.16%/g) 0.5 minutes after i.v. injection and eliminated by a fast and a slow phase. At the maximum of accumulation the brain/blood ratio was 1.21, decreasing to less than 0.15 already after one hour.
Authors:S. Reske, W. Sauer, H. Machulla, E. Knust, K. Reichmann, and C. Winkler
Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15/p-123I-phenyl-/pentadecanoic and l-14C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidneys, both tracers labelled nearly identical lipid fraction. Main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fraction indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying free fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated.
Authors:M. Figols, R. Gonçalves, E. Muramoto, S. Sato, D. Freire Martinez, M. Colturato, C. Gonçalves, and J. Knust
The described labelling and purification preparation of N-isopropyl-p-131I-amphetamine /131I-IMP/ represents a fast and efficient method to obtain a compound that fulfils all criteria of purity for its in-vivo application. After isotope exchange and quality control131I-IMP could be obtained with radiochemical yields in the range between 68% and 78% with a radiochemical purity of 98–99%. As demonstrated in animal experiments the cerebral affinity of IMP offers a possibility for the diagnosis of brain diseases in clinical studies when the product is labelled with123I.