Measurement of plasma metabolites of (S)-5-[123I]iodo-3- (2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

“…Chemicals used in radiolabelling and in autoradiography assays were obtained from Sigma Aldrich, UK and Vectabond was from Vector Labs, UK. Na 125 Zoghbi et al (2001). Aliquots (300 mg) of TMS precursor were stored in nitrogen-filled, silanized vials at À181C.…”

“…Modification of a previously reported method (Zoghbi et al, 2001) has allowed radiolabelling and purification of 5- 125 IA via a more rapid, one-pot synthesis method. 5-[ 125 I]-A-85380 was successfully obtained with a radiochemical purity of 498% and an isolated radiochemical yield of 60.2%.…”

Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT

“…In brief, subjects were pretreated with stable supersaturated potassium iodide (SSKI, 800 mg) and two antecubital venous catheters were placed prior to radiotracer injection. [ 123 I]5-IA was synthesized as previously described [43] and administered by a bolus (4.2 ± 0.5 mCi) followed by continuous infusion (0.6 ± 0.1 mCi/h) at a constant rate using a computer-controlled pump (IMED pump, Gemini PC-1, San Diego CA USA) for a bolus to infusion ratio of 7.0 h for 8 h. Thus, the total administered dose was 9.5 ± 1.1 mCi. Vital signs including blood pressure, heart and respiration rates were measured between 30-60 min pre and post Three consecutive 30-min emission scans and one 15-min simultaneous transmission and emission protocol scan (STEP) were acquired between 6 and 8 h of infusion on a Picker PRISM 3000XP (n=37) or 3000XP2 (n=10), three-headed camera (Philips Medical System, The Netherlands) equipped with low energy, ultra-high resolution fanbeam collimators (photopeak window 159 keV ± 10%; matrix 128 × 128).…”

“…The axial resolution (full width at half maximum) is 12.2 mm, measured with a 123 I line source in water in a cylindrical phantom. Plasma samples were collected immediately before and after the emission scans to quantify total parent tracer concentration and the free fraction (not protein bound) of parent tracer in plasma (f 1 ) [43].…”

Pharmacokinetic Modeling and [123I]5-IA-85380 Single Photon Emission Computed Tomography Imaging in Baboons: Optimization of Dosing Regimen for ABT-089

“…Specifically, PET/SPECT imaging has been increasingly exploited for dose selection or patient stratification in clinical studies of novel CNS treatments (Wong et al, 2009). To visualize nAChRs binding activity, several radiolabeled analogs of the high-affinity nicotinic ligand A-85380 [3-[2(S)-2-azetidinylmethoxy]pyridine] (Sullivan et al, 1996) have been developed as SPECT tracers Musachio et al, 1999;Zoghbi et al, 2001). In particular, 5-[ ]5-IA) has been extensively used as a SPECT radioligand for nAChRs.…”