Synthesis of N‐tert ‐butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) for in vivo detection of free radicals

We have synthesized the fluorine‐18 labeled derivative of N ‐ tert ‐butyl‐α‐phenylnitrone (PBN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N ‐ tert ‐Butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N ‐ tert ‐butyl‐α‐(4‐nitrophenyl)nitrone with [ 18 F]fluoride. An alternate two step synthesis route consisted of the nucleophilic [ 18 F]fluoride substitution of 4‐ N , N , N ‐trimethylammoniumbenzaldehyde triflate to yield 4‐[ 18 F]fluorobenzaldehyde, which was distilled into a vial containing N ‐ tert ‐butyl‐hydroxylamine in 2N NaOH. 4‐[ 18 F]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [ 18 F]FPBN. [ 18 F]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time < 45 min. and was suitable for further applications in in vivo studies of free radicals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90158/1/2580360202_ftp.pd

Synthesis of (N‐[ 11 C]methyl)Y‐29794, a competitive inhibitor of prolyl endopeptidase

Prolyl endopeptidase (PEP: [E.C.3.4.21.26]) is a widely distributed serine peptidase that cleaves a variety of oligopeptides in the brain and peripheral tissues. Y‐29794 ((2‐(8‐dimethylaminooctylthio)‐6‐isopropyl‐3‐pyridyl‐2‐thienyl ketone) is a potent competitive reversible inhibitor of this enzyme. In order to study the biodistribution of PEP in vivo we have synthesized (N‐[ 11 C]methyl)Y‐29794, by [ 11 C]alkylation of the N‐desmethyl precursor. The radiotracer was purified by silica gel Sep‐Pak and was obtained in 10‐17% yields (EOB: synthesis times shorter than 45 min) with >98% radiochemical purities and specific activities >550 Ci/mmol (EOS).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90219/1/2580340602_ftp.pd

Synthesis of [ 18 F]phencyclidines for glutamate receptor mapping

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90096/1/25802601150_ftp.pd

Extraction of [18F]fluoride from [18O]water by a fast fibrous anion exchange resin

[18F]Fluoride for nucleophilic radiofluorination was recovered from target water by trapping on a fibrous anion exchange resin in the hydroxide form and subsequent displacement into wet methanolic K2CO3. Extraction into methanol facilitated rapid evaporation and resolubilization of the [18F]fluoride as an ion pair. The resin was first dried in situ and rehydrated with [18O]H2O to avoid isotopic dilution of the target water.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28900/1/0000737.pd

Routine production of 2-deoxy-2-[18F]fluoro--glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin

Resin-supported [18F]fluoride ion has been prepared and applied to a rapid, convenient synthesis of [18F]FDG. "No-carrier-added" [18F]fluoride ion is collected on a quaternary 4-(N, N-dialkylamino)-pyridinium functionalized polystyrene anion exchange resin directly from a [18O]water target, dried by rinsing with acetonitrile, and then reacted with 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-[beta]--mannopyrannose. Acidic hydrolysis yields [18F]FDG in a synthesis time of 40 min with overall yields presently averaging above 50%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28859/1/0000694.pd

Mouse brain distribution of a carbon-11 labeled vesamicol derivative: Presynaptic marker of cholinergic neurons

The regional mouse brain distribution of a new carbon-11 labeled derivative of vesamicol, [11C]-5-(N-methylamino)benzovesamicol ([11C]MABV) is reported. Radiotracer concentrations in vivo are in the rank order of striatum&gt;cortex&gt;hippocampus&gt;hypothalamus&gt; cerebellum, consistent with reported distributions of other presynaptic cholinergic neuronal markers. In time course studies, striatum/cerebellum and cortex/cerebellum ratios for (-)-[11C]MABV continue to increase to values of 13 and 5, respectively, 75 min after i.v. injection of [11C]MABV. The specific binding in striatum and cortex is lowered by pretreatment with (+/-)-vesamicol, and shows stereoselectivity with lower uptake and lower ratios for the (+)-enantiomer. (-)-[11C]MABV is proposed as a positron-emitting radioligand for the in vivo study of presynaptic cholinergic neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28961/1/0000798.pd

Multiphase extraction: Rapid phase-transfer of [18F]fluoride ion for nucleophilic radiolabeling reactions

In multiphase extraction [18F]fluoride ion for radiolabeling is recovered from target water by passage through a small column of microporous polymer impregnated with a lipophilic cryptand or quaternary ammonium salt. The 18O enriched water can be recovered for reuse. The [18F]fluoride ion-pair is eluted from the column by a small volume of acetonitrile or other organic solvent. Evaporation of the acetonitrile removes traces of water to yield a reactive ion pair for nucleophilic radiofluorination reactions. A wide range of ion-pairs based on K+ or NH4+ cryptands or quaternary ammonium salts can be employed. The method was applied to the synthesis of [18F]FDG.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27603/1/0000647.pd

Super congruences and Euler numbers

Let $p>3$ be a prime. We prove that $$\sum_{k=0}^{p-1}\binom{2k}{k}/2^k=(-1)^{(p-1)/2}-p^2E_{p-3} (mod p^3),$$ $$\sum_{k=1}^{(p-1)/2}\binom{2k}{k}/k=(-1)^{(p+1)/2}8/3*pE_{p-3} (mod p^2),$$ $$\sum_{k=0}^{(p-1)/2}\binom{2k}{k}^2/16^k=(-1)^{(p-1)/2}+p^2E_{p-3} (mod p^3)$$, where E_0,E_1,E_2,... are Euler numbers. Our new approach is of combinatorial nature. We also formulate many conjectures concerning super congruences and relate most of them to Euler numbers or Bernoulli numbers. Motivated by our investigation of super congruences, we also raise a conjecture on 7 new series for $\pi^2$, $\pi^{-2}$ and the constant $K:=\sum_{k>0}(k/3)/k^2$ (with (-) the Jacobi symbol), two of which are $$\sum_{k=1}^\infty(10k-3)8^k/(k^3\binom{2k}{k}^2\binom{3k}{k})=\pi^2/2$$ and $$\sum_{k>0}(15k-4)(-27)^{k-1}/(k^3\binom{2k}{k}^2\binom{3k}k)=K.$

Iodine-125 and fluorine-18 labeled aryl-1,4-dialkylpiperazines: Potential radiopharmaceuticals for in vivo study of the dopamine uptake system

A series of fluorine-18 and iodine-125 labeled aryl-1,4-dialkylpiperazine analogs, derivatives of GBR 12935, were synthesized as radiotracers for positron emission tomography or single photon emission computerized tomography imaging of the brain based on their affinity for the presynaptic dopamine reuptake system. High specific activity fluorine-18 tracers were prepared by nucleophilic aromatic substitution reactions; iodine-125 tracers were prepared by isotopic exchange reactions. In vitro competitive binding studies demonstrated that iodine substitution is tolerated in the 4-position of the phenyl ring of the phenalkylpiperazine group. In vivo regional brain biodistribution studies in mice indicated no selectivity of the radioiodinated ligands for the dopamine reuptake site, with striatum/cerebellum concentration ratios of 1. Similar negative results with the new fluorine-18 derivatives demonstrated that in vivo selectivity for the dopamine reuptake site appears to be critically dependent on the carbon chain length between the piperazine ring and the solitary aromatic ring. These studies suggest that development of new radiopharmaceuticals based on the GBR 12935 structure cannot be based solely on considerations of in vitro binding affinities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30090/1/0000461.pd

A captive solvent method for rapid N-[11C]methylation of secondary amides: Application to the benzodiazepine, 4'-chlorodiazepam (RO5-4864)

[11C]4'-Chlorodiazepam (RO5-4864), for PET studies of peripheral benzodiazepine receptors, was synthesized by alkylation of 1-desmethyl-4'-chlorodiazepam, in a small volume of acetone adsorbed on acrylic yarn, with [11C]methyl iodide in the injection loop of a liquid chromatograph. The reaction mixture was introduced directly onto a small, disposable alumina chromatographic column. Elution with pentane:ethanol gave a product of high chemical and radiochemical purity. A simple heating and cooling device for the injection loop is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27565/1/0000609.pd