ASN004, A 5T4-targeting scFv-Fc Antibody-Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models.

The 5T4 oncofetal antigen (trophoblast glycoprotein) is expressed in a wide range of malignant tumors but shows very limited expression in normal adult tissues. ASN004 is a 5T4-targeted antibody-drug conjugate (ADC) that incorporates a novel single-chain Fv-Fc antibody and Dolaflexin drug-linker technology, with an Auristatin F hydroxypropylamide payload drug-to-antibody ratio of approximately 10-12. The pharmacology, toxicology, and pharmacokinetic properties of ASN004 and its components were investigated and ASN004 showed high affinity for the 5T4 antigen and was selectively bound to and internalized into 5T4-expressing tumor cells, and potent cytotoxicity was demonstrated for a diverse panel of solid tumor cell lines.

Annular Elastolytic Giant Cell Granuloma.

Annular elastolytic giant cell granuloma (AEGCG) is a rare, often self-limiting chronic inflammatory disorder mostly occurring in the sun-exposed areas such as the dorsum of hands, extensor surfaces of arms, face, anterior neck, and upper chest. The pathognomonic histological findings include the presence of numerous granulomas associated with loss of elastic fibers that appear to be ingested by multi-nucleated giant cells. Here, we present a case of a 56-year-old woman with multiple, anatomically variable erythematous lesions- annular and papular, mainly in the upper body.

Assessment of 18F-labeled mitochondrial complex I inhibitors as PET myocardial perfusion imaging agents in rats, rabbits, and primates.

Purpose: Myocardial extractions of mitochondria complex I (MC-I) inhibitors were high and well correlated with flow. This study assessed the potential of MC-I inhibitors to be developed as myocardial perfusion imaging (MPI) agents.

Methods: RP1003, RP1004, and RP1005 representing three classes of MC-I inhibitor were synthesized and radio-labeled with (18)F.

BMS-747158-02: a novel PET myocardial perfusion imaging agent.

Background: BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents.

Methods And Results: In a rat biodistribution study, BMS-747158-02 (15 microCi) had substantially higher myocardial uptake than technetium 99m sestamibi (100 microCi) at 15 minutes (3.

Quinazoline derivatives as MC-I inhibitors: evaluation of myocardial uptake using Positron Emission Tomography in rat and non-human primate.

Several quinazoline derivatives were made as mitochondrial complex 1 inhibitors. Compound 4 showed an IC(50) of 11.3 nM and was the most potent compound of this series.

Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats.

Background: Dahl salt-sensitive (Dahl S) rats exhibit many phenotypic traits associated with salt-sensitive hypertension in man. Specifically, they are salt-sensitive, insulin-resistant and hyperlipidemic. They also develop endothelial dysfunction, cardiac injury and glomerulosclerosis.

Renal effects of glucagon-like peptide in rats.

The present study examined the effects of recombinant glucagon-like peptide-1-(7-36)amide (rGLP-1) on renal hemodynamics and excretory function in innervated and denervated kidneys of anesthetized rats. Intravenous infusion of rGLP-1 at a dose of 1 microg x kg(-1) x min(-1) increased urine flow and Na(+) excretion 13-fold in the innervated kidney. The natriuretic and diuretic response to rGLP-1 was attenuated in the denervated kidney in which urine flow and Na(+) excretion only increased 3-fold.