Potential Brain Imaging Agent Research Articles

Synthesis and preliminary evaluation of L‐6‐[123I]Iododopa as a potential spect brain imaging agent

AbstractL‐6‐[123I]Iododopa was synthesized by the exchange of 123I for bromine on L‐6‐bromodopa in buffer(pH 4) for 35 minutes at 97°C. The synthesis was complete in approximately 1 hour with a radiochemical yield of 50%, a specific activity of 65 Ci/mmol and a radiochemical purity of ≥95%. A non radioactive standard of L‐6‐iododopa was synthesized by the iododemercuration of a mercury‐dopa derivative using I2 in chloroform. It was shown that L‐6‐[123I]iododopa accumulated in the rat striatum with striatum:whole brain ratio of 1.36 at 1 hour and 1.11 at 2 hours.

Radioiodinated phenoxyacetic acid derivatives as potential brain imaging agents. I. Efficient synthesis via trimethylsilyl intermediates.

The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. 125I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a--e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a--c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a--e, 6a--c, 8, 13, 17) by this method.

Radioiodinated phenoxyacetic acid derivatives as potential brain imaging agents. II. Structure-biodistribution relationship.

In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The alpha, alpha-dimethylester derivative (1e), amide derivatives (2a--c) and diamine derivatives (3a, b, 4), which were stable to hydrolysis, showed low blood activity levels following i.v. administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential brain imaging radiopharmaceuticals with SPECT devices.

Synthesis and biodistribution of labelled p-iodo phentermine (IP), N,N,-dimethyl-p-iodo phentermine (IDMP) and N-isopropyl-p-iodo phentermine (IIP) in rats.

p-Iodo-phentermine (IP) and two of its derivatives, N,N,-dimethyl-p-iodo-phentermine (IDMP) and N-isopropyl-p-iodo-phentermine (IIP) were synthesized and radiolabelled with iodine by isotopic exchange. They were evaluated as potential brain imaging agents and compared to IAMP biodistribution in rats did not show any superiority to IAMP.

Radioiodinated I -substituted-4-phenylpiperazines as potential brain imaging agents

A series of four 125I-labeled 1-substituted-4-phenylpiperazines were prepared and evaluated in rats as potential brain imaging agents. The compounds were labeled using [125I]iodide/chloramine-T or iodine monochloride and isolated in 48–60% radiochemical yields. The tissue distribution studies indicated that a butyrophenone derivative demonstrated the best overall brain-imaging properties. Compared with the compounds having other 1-substituents this agent had a more prolonged retention of activity in the brain and higher brain-to-blood ratios over the 4-h period studied. The in vivo behavior of this agent is comparable to that of radioiodinated N-isopropyl-p-iodoamphetamine, and, because it can be labeled directly via electrophilic methods, it has substantial potential for use in brain imaging with single photon emission computed tomography.

Radioiodinated 1 -(diethylaminopropyl)-4-phenylpiperazine: A potential brain imaging agent

The preparation of radioiodinated 1-(diethylaminopropyl)-4-phenylpiperazine, an analog of HIPDM, and its tissue distribution in rats are described. The precursor undergoes facile electrophilic radioiodination with radionuclides of iodine at the no-carrier-added level to give isolated yields in the 69-85% range. Biodistribution studies indicate that the radiochemical is well extracted by the brain (1.68-1.79% ID) and activity is substantially retained for 4 h (greater than 67%). Brain-to-blood ratios during the 0.25-4.0 h period were 15-23:1. The brain uptake and retention as well as the high brain-to-blood ratios suggest the potential use of this agent for regional cerebral blood flow imaging.

Preparation and evaluation of 3-[ 125I]iodo-4-aminophentermine as a brain perfusion imaging agent. Comparison with labeled phentermine derivatives

A radioiodinated derivative of the anorexinergic drug phentermine was synthesized and evaluated as a potential brain imaging agent. Stoichiometric iodination of the intermediate 4-aminophentermine (AmP) gave a mixture of mono and diiodo products, while the radioiodination at the no-carrier-added (NCA) level gave 73% isolated yield of the 3-[ 125I]iodo-4-aminophentermine with less than 2% of the diiodo derivative. The tissue distribution of the radiochemical in rats showed that it was readily extracted by the brain followed by relatively slow clearance from that organ. However, a comparison with other labeled phentermine derivatives indicated that the total brain uptake, retention and selectivity of the new agent were poorer, probably as a result of the presence of the 4-amino substituent.

Synthesis and tissue distribution study of iodine-labeled benzyl- and xylylamines

Four iodine-125 labeled mono- and diamines were prepared and evaluated as potential brain-imaging agents. The diamines are analogues of the previously reported selenium-75 labeled diamines, which show high brain uptake and retention. All of the radioiodinated amines display high initial brain uptake in rats after intravenous injection (1.7-2.4% dose/organ). The xylylenediamines show prolonged brain retention (t1/2 approximately 18 h), which is desirable for brain imaging. In contrast, the benzylamine is rapidly cleared from brain tissue (t1/2 approximately 15 min).

131I-labelled N-isopropyl-p-Iodoamphetamine.

Synthesis of N-isopropyl-p-iodoamphetamine from the readily available phenylacetic acid is described. The product has been characterized by elemental analysis, mass spectroscopy and 1H-nuclear magnetic resonance. The potential brain imaging agent N-isopropyl-p-iodo (131)amphetamine was prepared by exchange labelling in weakly acidic aqueous solution in the presence of Cu(II).