Structure-activity relationship studies on an antitumor marine macrolide using aplyronine a-swinholide A hybrid.

An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein-protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The importance of the methoxy group in the ,,-trimethylserine ester was clarified by the structure-activity relationship studies of the amino acid moiety by using the hybrid analogs.

Site-selective C-H borylation of quinolines at the C8 position catalyzed by a silica-supported phosphane-iridium system.

Site-selective C-H borylation of quinoline derivatives at the C8 position has been achieved by using a heterogeneous Ir catalyst system based on a silica-supported cage-type monophosphane ligand SMAP. The efficient synthesis of a corticotropin-releasing factor1 (CRF1) receptor antagonist based on a late-stage C-H borylation strategy demonstrates the utility of the C8 borylation reaction.

Fluorodeoxyglucose accumulation in the left atrial appendage of a patient with paroxysmal atrial fibrillation.

A 69-year-old man with a history of paroxysmal atrial fibrillation (PAF) and subsequent cerebral infarction was referred to our hospital because of an abnormal accumulation of F-fluorodeoxyglucose (FDG) in the left atrial appendage (LAA) that was detected on positron emission tomography-computed tomography (PET-CT) imaging during a health screening. Transesophageal echocardiography (TEE) demonstrated thrombus formation in the LAA. Even after the thrombus disappeared by strictly guided oral anticoagulant therapy, intense abnormal FDG uptake in the LAA on PET-CT imaging persisted.

Prediction of myelotoxicity based on bone marrow radiation-absorbed dose: radioimmunotherapy studies using 90Y- and 177Lu-labeled J591 antibodies specific for prostate-specific membrane antigen.

Unlabelled: In radioimmunotherapy, myelotoxicity due to bone marrow radiation-absorbed dose is the predominant factor and frequently is the dose-limiting factor that determines the maximum tolerated dose (MTD). With (90)Y- and (131)I-labeled monoclonal antibodies, it has been reported that myelotoxicity cannot be predicted on the basis of the amount of radioactive dose administered or the bone marrow radiation-absorbed dose (BMrad), estimated using blood radioactivity concentration. As part of a phase I dose-escalation study in patients with prostate cancer with (90)Y-DOTA-J591 (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) ((90)Y-J591) and (177)Lu-DOTA-J591 ((177)Lu-J591), we evaluated the potential value of several factors in predicting myelotoxicity.

Pharmacokinetics and biodistribution of 111In- and 177Lu-labeled J591 antibody specific for prostate-specific membrane antigen: prediction of 90Y-J591 radiation dosimetry based on 111In or 177Lu?

Unlabelled: 111In-Labeled antibodies and peptides have been routinely used as chemical and biologic surrogates for 90Y-labeled therapeutic agents. However, recent studies have shown that there are significant differences in biodistribution between 111In- and 90Y-labeled agents. Yttrium and lutetium metals favor the +3 oxidation state, similar to indium, but there are minor differences in the solution and coordination chemistries among these metals.

Determination of immunoreactive fraction of radiolabeled monoclonal antibodies: what is an appropriate method?

Determination of the immunoreactive fraction (IF) of radiolabeled monoclonal antibodies (MAb) is essential to the understanding of the effects of radiolabeling and subsequent target-specific tumor localization. There has been generally no accepted method of determining the IF of MAbs. The conventional method is based on a radioimmunoassay technique in which the fraction of radiolabeled MAb bound to antigen under conditions of "antigen excess" is determined.

Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate early after their sectorial resection.

Unlabelled: The aim of the present study was to investigate asialoglycoprotein receptor (ASGP-R) status in tumor-bearing livers and early after their sectorial resection employing 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) dynamic SPECT.

Methods: Ten normal liver controls and 44 liver tumor patients who underwent sectorial hepatectomy were included in the study. 99mTc-GSA dynamic SPECT study was performed 7 +/- 3 d before (pre-operative) and 34 +/- 13 d after surgery (post-operative) in liver tumour patients.

Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.

Unlabelled: Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth.

Radionuclide cisternography in intracranial hypotension syndrome.

A 44-year-old male patient complaining of severe headache right after twisting his body during aerobic exercises in a swimming pool underwent In-111 DTPA radionuclide cisternography. Leakage of cerebrospinal fluid (CSF) was proved on the right side of T2 and T3 vertebrae. Cisternography after bed and conservative treatments demonstrated the disappearance of abnormal tracer accumulations.