Re(CO)([F]FEDA), a novel F PET renal tracer: Radiosynthesis and preclinical evaluation.

Introduction: Our previous work demonstrated that the Tc renal tracer, Tc(CO)(FEDA) (Tc-1), has a rapid clearance comparable in rats to that of I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of Tc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl F renal imaging agent, Re(CO)([F]FEDA) (F-1). Our goal was to develop an efficient one-step method for the preparation of F-1 and to compare its pharmacokinetic properties with those of I-OIH in rats.

Synthesis and biological properties of radiohalogenated α,α-disubstituted amino acids for PET and SPECT imaging of amino acid transporters (AATs).

Fluorine-18 and iodine-123 labeled nonnatural alicyclic and methyl branched disubstituted α,α-amino acids are a diverse and useful class of tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased expression of the cell membrane amino acid transporter systems L, ASC, and A exhibited by many human tumor cells. The most established clinical use for these radiolabeled amino acids is imaging primary and recurrent gliomas and primary, recurrent, and metastatic prostate cancer.

Test-Retest Reliability of the SERT Imaging Agent C-HOMADAM in Healthy Humans.

The aim of this study was to measure the test-retest reliability of C--dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine (C-HOMADAM) imaging of serotonin transporter (SERT) density in healthy control subjects. Two female and 2 male volunteers participated in the study, with each undergoing three 90-min C-HOMADAM PET scans. Time-activity curves were derived from SERT-rich structures and fit to 2 models: a simplified reference tissue model and a multilinear graphical model.

Monoanionic Tc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers.

Introduction: Tc(CO)-nitrilotriacetic acid, Tc(CO)(NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of I-OIH but the clearance of Tc(CO)(NTA) and I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic Tc(CO)(NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the Tc(CO)(NTA) metal-coordination sphere but with uncharged pendant groups.

Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.

[(18)F]2-Fluoroethyl-p-toluenesulfonate also called [(18)F]2-fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [(18)F]2-Fluoroethyl-4-bromobenzenesulfonate, also called [(18)F]2-fluoroethyl brosylate ([(18)F]F(CH2)2OBs), was used as an alternative radiolabeling agent to prepare [(18)F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O-fluoroethylating the phenolic precursor. Purified by reverse-phase HPLC, the no-carrier-added [(18)F]F(CH2)2OBs was obtained in an average radiochemical yield (RCY) of 35%.

Fluorinated diaryl sulfides.

Diaryl sulfides also known as diphenyl sulfides, phenylthiobenzylamines, and biphenylthiols are a class of compounds with phenylthiophenyl scaffold that have been validated as biomarkers to label the brain serotonin transporter (SERT), in vivo. The development of those synthetic and non-natural compounds started more than a decade ago when the observation that 5-chloro-((2-((dimethylamino)methyl)phenyl)thio)benzene-methanol hydrochloride also called 403U76 inhibited the serotonin and norepinephrine uptake into rat brain synaptosomes, led to the preparation of few derivatives based on 403U76 chemical structure. The new class of compounds, called the diaryl sulfide family, was investigated as biomarkers for the brain SERT.

Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid.

Introduction: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[(18)F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[(18)F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans.

Methods: A DU145 xenograft rodent model was used to measure anti-2-[(18)F]FACPC-1 uptake at 15, 30 and 60 min post-injection.

Pilot evaluation of anti-1-amino-2-[18F] fluorocyclopentane-1-carboxylic acid (anti-2-[18F] FACPC) PET-CT in recurrent prostate carcinoma.

Purpose: Anti-1-amino-2-[(18)F]fluorocyclopentane-1-carboxylic acid (anti-2-[(18)F]FACPC) is an unnatural alicyclic amino acid radiotracer with high uptake in the DU-145 prostate cancer cell line in vitro. Our goal was to determine if anti-2-[(18)F]FACPC is useful in the detection of prostate carcinoma.

Procedures: Five patients with elevated PSA (1.