Development of radioiodinated lipophilic cationic compounds for myocardial imaging

IntroductionTc-99m compounds are mainly used in myocardial blood flow studies. These compounds, however, are produced by a generator and alternate single photon emission computed tomography (SPECT) radiopharmaceuticals are therefore required to avoid the risks posed by generator failure. Three radiolabeled compounds, including [125I]p-iodobenzyl triphenylphosphonium ([125I]ITPP), [125I]p-Iodobenzyl dipropylphenylphosphonium ([125I]IDPP) and [125I]p-iodobenzyl methyldiphenylphosphonium ([125I]IMPP), have been synthesized in the current study. All three of these compounds contain a lipophilic cation, which enhances their cell permeability properties and allows them to accumulate in the myocardium as SPECT probes.Methods4-(2-Tributylstannyl) benzyl alcohol was mixed with [125I]NaI in the presence of aqueous hydrogen peroxide and hydrochloric acid to allow for the synthesis of 4-[125I]iodobenzyl alcohol. Bromination of the alcohol under standard conditions gave 4-[125I]iodo benzyl bromide, which was treated with triphenylphosphine, dipropylphenylphosphine or methyldiphenylphosphine to give [125I]ITPP, [125I]IDPP and [125I]IMPP, respectively. These compounds were evaluated in biodistribution and SPECT studies in normal ddY mice.ResultsAll three of the radiolabeled compounds were synthesized in approximately 60% yield with radiochemical purities greater than 99%. The specific activity of each compound was 74 GBq/μmol. The results of the biodistribution and SPECT studies showed that all compounds accumulated preferentially in the heart in vivo, especially [125I]IDPP.Conclusion[123I] IDPP could be used in clinical practice as a novel myocardial imaging agent.