D.N. Abrams

Production of 34m Cl from a gaseous hydrogen sulfide target

Abstract The production and recovery of 34 m Cl, from a gaseous hydrogen sulfide target, in a chemical form suitable for labelling radiotracers is described. The 34 m Cl was produced via the 34 S(p,n) 34 m Cl (22 MeV protons) and 34 S(d, 2n) 34 m Cl (12 MeV deuterons) nuclear reactions using natural isotopic abundance H 2 S (target pressue 400 kPa; target dimensions 40 × 3 cm i.d.). 34 m Cl was recovered in yields of 13.0 MBq μ A −1 h −1 and 0.54 MBq μA −1 h −1 respectively, as chloride anion on an anion exchange resin. The utility of the recovered 34 m Cl for the synthesis of 34 m Cl labelled radiotracers was demonstrated by the synthesis of 2′-[ 34 m Cl]-2′-chloro-2′-deoxyuridine in 34.5% radiochemical yield.

Synthesis and evaluation of novel 4-amino-4,6-androstadiene-3,17-dione : An analog of formestane

Synthesis of 4-amino-4,6-androstadiene-3,17-dione 7, an analog of formestane used in breast cancer therapy as an aromatase inhibitor, from 4-acetoxy-4-androstene-3,17-dione 2 is described. This is the first report of a 4-amino diene (4,6) system in this series of molecules. The new (7) and reported molecules were screened by the National Cancer Institute (NCI, Bethesda, USA) for in vitro antitumor activity against 60 human cancer cell lines. Molecule 7 showed best activity against breast cancer cell line (MCF-7).

Tumour uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models—IV. 2′-123I-iodo-2′-deoxyuridine

Iodine-123 was produced via the 124Te(p,2n)123I reaction by irradiating an enriched TeO2 target, using the DKFZ Heidelberg compact cyclotron. Radioiodine recovered from the target by sublimation was exchanged into carrier NaI, and reacted with 2,2′-anhydrouridine in dioxane and catalytic amounts of trifluoroacetic acid for 25 min at 135°C, to produce 2′-123I-iodo-2′-deoxyruridine. Radiochemical yields were as high as 84% with specific activities estimated at 17 Ci mmol−1. Tissue distribution and excretion studies after i.v. injection of 2′123I-iodo-2′-deoxyuridine into Wistar rats bearing Walker 256 carcinomas indicated limited tissue uptake and rapid urinary excretion. Only thyroid, kidneys, stomach and liver accumulated radioactivity. 90% of the i.v. dose was excreted in the urine, with 39% of the dose present as unchanged 2′-123I-iodo-2′-deoxyuridine.

The synthesis of radiolabelled 1-(2′-Fluoro-2′-deoxy-β-D-ribofuranosyl)-uracil and 1-(2′-chloro-2′-deoxy-β-D-ribofuranosyl)uracil

Radiolabelled derivatives of 1-(2′fluoro-2′-deoxy-β-D-ribofuranosyl)uracil 3 (2′-FUdR) and 1-(2′-chloro-2′-deoxy-β-D-ribofuranosyl)uracil 4 (2′-ClUdR) were synthesized for evaluation as diagnostic radiopharmaceuticals. 6-[3H]-2′-FUdR (21% radiochemical yield from 6-[3H]-uridine; 4.26 GBq mmol−1) and 2-[14C]-2′-FUdR (25% radiochemical yield; 1.85 GBq mmol−1 were prepared by reaction of anhydrous hydrogen fluoride (AHF) with 6-[3H]- or 2-[14C]-labelled 2,2′-anhydro-1-β-D-arabinofuranosyluracil 2 (2,2′-AUR). 6-[3H]-2′-ClUdR (53% radiochemical yield; 11.1 GBq mmol-t-1) was prepared by reaction of CaCl2 with 6-[3H]-2,2′-AUR. Reaction of [18F]-AHF with 2,2′-AUR afforded 2′-[18F]-2′-FUdR in low radiochemical yield while reaction of 2,2′-AUR with [36Cl]-NaCl and trifluoroacetic acid gave 2′-[36Cl]-2′-ClUdR (30% radiochemical yield; 5.46 MBq mmol−1). 2′-[34mCl]-2′-ClUdR was similarly prepared using [34mCl]-MgCl2 or [34mCl]-Dowex 21-K resin in 2.7% (16.8 MBq mmol−1) and 36% (0.304 GBq mmol−1) radiochemical yield respectively.

New Short Synthesis of (5)‐2,3‐Dimethoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐iodobenzamide: Dopamine D2 Receptor

Abstract A new short and highly efficient synthesis of (5)‐2,3‐dimethoxy‐N[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐iodobenzamide (epidepride, 1) from 3‐methoxy‐salicylaldehyde (o‐vanillin, 2) and 3‐methoxysalicyclic acid (6) was achieved by employing a new iodination method with iodine monochloride and iodine nitrate under basic conditions.Abstract A new short and highly efficient synthesis of (5)‐2,3‐dimethoxy‐N[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐iodobenzamide (epidepride, 1) from 3‐methoxy‐salicylaldehyde (o‐vanillin, 2) and 3‐methoxysalicyclic acid (6) was achieved by employing a new iodination method with iodine monochloride and iodine nitrate under basic conditions.

Tumor uptake of radiolabeled pyrimidine bases and pyrimidine nucleosides in animal models--II. 6-[3H]-5-fluoro-2'-deoxyuridine.

Abstract The tissue distribution and urinary excretion of i.v. doses of 2′-[ 82 Br]-bromo-2′-deoxy-uridine (2′-[ 82 Br]-UdR) have been studied in BDF 1 mice bearing subcutaneous Lewis Lung carcinomas. No tissue accumulated radioactivity to a greater concentration (cpmg −1 ) than whole blood, and elimination occurred primarily via the urine although some radioactivity was present in bile shortly after injection. Analysis of whole-body elimination data, and comparison of this data with that for i.v. doses of NH 4 82 Br, showed that 55% of the radioactivity from a dose of 2′-[ 82 Br]-UdR was eliminated in the form of the Br anion. Whole-body elimination of radioactivity from a single dose of 2′-[ 82 Br]-UdR followed 2-compartment kinetics with half-lives of 3 and 30 h; NH Br elimination could be described as a single exponential function with a 30-h half-life.

Separation of [(99m)Tc]pertechnetate and molybdate using polyethylene glycol coated C18 and C30 resins.

Hydrophobic adsorbents such as C18 and C30 were coated with PEG and subsequently used for the separation of Mo/Tc. The most effective resin for adsorbing PEG was the C18-U resin, which demonstrated a coating capacity of 97.6±2.8mg PEG per g of resin. The ability to adsorb pertechnetate was proportional to the amount of PEG coated on the hydrophobic resin. The [(99m)Tc]pertechnetate recovery during the separation of cyclotron produced (99m)Tc from (100)Mo was 91.8±0.3% (n=2). The resultant product met relevant USP monograph specifications.

Tumor uptake of radiolabeled pyrimidine bases and pyrimidine nucleosides in animal models—I. 6-[3H]-5-fluorouracil

Abstract The differential tissue distribution and urinary excretion of small intravenous doses (4 μg kg −1 ) of 6-[ 3 H]-5-fluorouracil have been studied in two strains of mice bearing transplantable tumors. The subcutaneous Lewis Lung carcinoma and the solid Ehrlich Ascites carcinoma both retained less than 1.5% of the dose, and for all tissues assayed the tumor: blood ratios for radioactivity were 11:1 or less. Approximately 75% of the injected dose was excreted during the first 12 h. Urinary excretion was resolved using a two-compartmental model. The half-life of the fast component was just over 1 h while that for the slow component was in excess of 10 days.

Synthesis of [6-36Cl]chlorouracil, [6-82Br]bromouracil and [6-123I]iodouracil☆

Abstract Three C-6 radiohalogenated uracil derivatives were prepared by non-isotopic halogen exchange reactions for evaluation as diagnostic radiopharmaceuticals. [6- 36 Cl]chlorouracil (radiochemical yield 77%, specific activity 5.66 MBq mmol −1 ) was prepared via calcium [ 36 Cl]chloride exchange on 6-iodouracil, [6- 82 Br]bromouracil (27%, 68.4 MBq mmol −1 ) was prepared via ammonium [ 82 Br]bromide exchange on 6-iodouracil and [6- 123 I]iodouracil (55.4%, 5.41 GBq mmol −1 ) was prepared via sodium [ 123 I]iodide exchange on 6-chlorouracil. The specific activities and radiochemical yields were dependent upon the halide-ion concentration.

Review: Technegas - 99mTc-Metal Core Graphite Nanoparticles for Pulmonary Ventilation Imaging

Technegas, a carbon-coated Tc-99m nanoparticulate aerosol invented by Burch at the Australian National University in 1984, was introduced to the medical community in 1986 with two reports of its use as a new ventilation agent for lung imaging. Since that time, more than 1,500 Technegas machines have been distributed in hospitals and clinics in 54 countries, and more than 2 million Technegas ventilation studies have been completed. This review provides a synopsis of the more than 250 publications, abstracts and reports on Technegas. Technegas compares favourably with other commonly used ventilation (V) imaging agents including Xenon-133 and Krypton-81m gases, and several technetium-99m aerosol formulations. It is an effective agent for pulmonary ventilation (V) studies, particularly for detecting pulmonary embolisms when used in combination with perfusion (Q) scintigraphy by a technique known as ventilation/local perfusion image-mismatch (V/Q) imaging. Other applications for Technegas include non-clinical V/Q imaging in large animals, gastric emptying studies with Technegas-labeled meals, powder formulation studies of Technegas-labeled drugs, thrombosis detection using a precipitated formulation of Technegas (Thrombotrace) and pulmonary clearance studies using a derivative form called Pertechnegas.