[123I]CLINDE

[123I]CLINDE (also known as 123I-CLINDE) is a radioiodinated imidazopyridine-3-acetamide compound used as a diagnostic radiopharmaceutical. It's specifically designed to bind to peripheral benzodiazepine receptors (PBR), which are also known as translocator protein (TSPO)[1][4]. ## Chemical Structure and Properties The full chemical name of [123I]CLINDE is 6-Chloro-2-(4'-[123I]iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide[1]. It has high selectivity for peripheral benzodiazepine receptors with an IC50 value of 1.7 nM for PBRs compared to 360 nM for central benzodiazepine receptors (CBRs)[1][2][4]. The compound has a log P value of 3.1 at pH 7.4, indicating its lipophilicity[1]. This property is important for its ability to cross biological membranes, including the blood-brain barrier. ## Synthesis and Preparation [123I]CLINDE is synthesized through 123I-iodination of a tributyltin precursor using Na123I. The compound is purified using high-performance liquid chromatography (HPLC). The radiochemical yield is typically between 75-85%, with a radiochemical purity exceeding 95%. The specific activity is greater than 185 GBq/μmol (5 Ci/μmol)[1]. ## Pharmacological Properties ### Binding Characteristics In vitro studies have demonstrated that [123I]CLINDE binds with high affinity to PBRs in various tissues: - Adrenal mitochondrial membranes: Kd = 12.6 nM, Bmax = 163 pmol/mg protein - Kidney mitochondrial membranes: Kd = 0.20 nM, Bmax = 5.3 pmol/mg protein - Brain cortex mitochondrial membranes: Kd = 3.84 nM, Bmax = 0.34 pmol/mg protein[1][4] ### Biodistribution In vivo biodistribution studies in rats have shown high uptake in several organs: - Adrenals: 5.4% ID/g at 6 hours post-injection - Heart: 1.5% ID/g at 6 hours post-injection - Lungs: 1.5% ID/g at 6 hours post-injection - Kidney: 1.5% ID/g at 6 hours post-injection[4] In the central nervous system, the olfactory bulbs showed the highest uptake, with activity up to six times that found in blood[4]. ## Diagnostic Applications [123I]CLINDE is designed for use in Single-Photon Emission Computed Tomography (SPECT) and planar gamma imaging[1]. It's being developed as a diagnostic tool for imaging PBRs, which are upregulated in various neuroinflammatory conditions. The compound shows potential applications in: 1. Neuroinflammatory disorders 2. Neurodegenerative diseases such as Parkinson's disease[6] 3. Multiple sclerosis/Neuromyelitis optica[6] ## Radiation Dosimetry Radiation dosimetry studies have been conducted to estimate the radiation dose to humans based on biokinetics in rat models. These studies involved administering [123I]CLINDE (0.75 MBq) intravenously to adult Sprague-Dawley rats and measuring activity concentrations in various organs and tissues[2]. ## Selectivity and Specificity Competition studies have demonstrated the selectivity of [123I]CLINDE for PBRs. Pre-administration of PBR-specific drugs like PK11195 and Ro 5-4864 significantly reduced the uptake of [123I]CLINDE in various tissues, while the central benzodiazepine receptor-specific drug Flumazenil had no effect on uptake[4]. Metabolite analysis has shown that more than 90% of the radioactivity in tissues remains as intact [123I]CLINDE, indicating good metabolic stability[4].

Other names

123I-CLINDE6-Chloro-2-(4'-[123I]iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide