Development of radioiodinated lipophilic cationic compounds for myocardial imaging.
BACKGROUND
Tc-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 [(125)I]p-iodobenzyl triphenylphosphonium ([(125)I]ITPP), [(125)I]p-Iodobenzyl dipropylphenylphosphonium ([(125)I]IDPP) and [(125)I]p-iodobenzyl methyldiphenylphosphonium ([(125)I]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.


METHODS
4-(2-Tributylstannyl) benzyl alcohol was mixed with [(125)I]NaI in the presence of aqueous hydrogen peroxide and hydrochloric acid to allow for the synthesis of 4-[(125)I]iodobenzyl alcohol. Bromination of the alcohol under standard conditions gave 4-[(125)I]iodo benzyl bromide, which was treated with triphenylphosphine, dipropylphenylphosphine or methyldiphenylphosphine to give [(125)I]ITPP, [(125)I]IDPP and [(125)I]IMPP, respectively. These compounds were evaluated in biodistribution and SPECT studies in normal ddY mice.


RESULTS
All 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 [(125)I]IDPP.


CONCLUSIONS
[(123)I] IDPP could be used in clinical practice as a novel myocardial imaging agent.
Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Toshihiro
T
Sakai
Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Yuriko
Y
Saito
Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Misato
M
Takashima
Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Mikako
M
Ogawa
Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: magata@hama-med.ac.jp.
Yasuhiro
Y
Magata
D000818:Animals; D055808:Drug Discovery; D004355:Drug Stability; D006321:Heart / Q000000981:diagnostic imaging*; D057927:Hydrophobic and Hydrophilic Interactions; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D007457:Iodine Radioisotopes; D009943:Organophosphorus Compounds
Cationic compound; Myocardial blood flow; Phosphonium ion; Radioiodine; SPECT