No abstract

The bifunctional chelating agents N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4-aminophenyl)methyl]-diethylenetriamine and N,N,N',N'',N''-pentakis(carboxymethyl)-1-[(4-aminophenyl)methyl]-4- methyldiethylenetriamine were prepared in six-step syntheses in overall yields of 38% and 31%, respectively. The use of bromoacetate esters in the synthesis allowed large-scale flash chromatographic purification of reaction products. The synthesis of N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4-aminophenyl)-methyl]-4-methyldiethylenetriamine resulted in a mixture of two diastereomers. Chelation of yttrium-(III) with these bifunctional chelating agents resulted in 1:1 chelates. In the case of N,N,N',N'',N''-pentakis(carboxymethyl)-1-[4- aminophenyl)methyl]diethylenetriamine, two diastereomers were observed upon chelation, as expected. In the case of N,N,N',N'',N''- pentakis(carboxymethyl)-1-[(4-aminophenyl)-methyl]-4- methyldiethylenetriamine, only three of the four anticipated diastereomers were observed.

Lutetium‐177 (177Lu), samarium‐153 (153Sm), and yt‐trium‐90 (90Y) are members of the family of elements known as lanthanides or rare earths. Monoclonal antibody CC49, a murine immunoglobulin (Ig) G1, which is reactive with the tumor‐associated antigen TAG‐72, previously has been shown to react with a wide range of human carcinomas. The authors review here the comparative biodistributions of CC49 IgG and F(ab′)2 fragments labeled with 177Lu, 153Sm, and 90Y using the bifunctional chelating agent PA‐DOTA. The authors also review the results of a biodistribution study comparing iodine‐125‐labeled and 177Lu‐labeled CC49 sFv, and the use of 177Lu‐CC49 IgG in an experimental therapy model. Chelation and conjugations gave similar yields, and the labeled proteins showed similar retention of immunoreactivity regardless of the isotope used for both IgG and F(ab′)2. Biodistribution data obtained in athymic mice bearing LS‐174T human colon carcinoma xenografts likewise showed no differences among the three radioisotopes for both IgG and F(ab′)2. Femur uptake of radioactivity was lower than previously reported for other radiolanthanide immunoconjugates. Different metabolic patterns were observed for radioiodinated versus radiometal‐la‐beled sFv, particularly in the kidney, where localization of the latter was increased dramatically. 177Lu‐CC49 was found to delay the growth of established LS‐174T human colon carcinomas in athymic mice at a single dose of 50 μCi. Elimination of established tumors was demonstrated over the observation period (77 days) using single administrations of 200 or 350 μCi. Dose fractionation experiments revealed that the mice tolerated 750 μCi (3 × 250 μCi, given weekly), whereas > 50% of the mice died after receiving a single administration of ∼ 500 μCi. In iso‐type‐matched control experiments, a large differential in the therapeutic effects was observed between 177Lu‐la‐beled control antibody and CC49. Cancer 1994; 73:993–8.

Fluorescence at room temperature and 77 K and phosphorescence a t 77 K have been observed from the complexes [fiz(t-BuNC)4(dPm)d (pF6)2, [fi2(n-BuNC)ddPm)d (BPh4)2, [fi2(PhNC).ddPm)2] (pF6)2, and [ W W u N C ) 4 ( d a m ) 2 1 (BPhJ2 [dpm = bis(diphenylphosphino)methane, dam = bis(diphenylarsino)methane] . The terms assigned to these emissions, lBlu and 3Blu, respectively, were also observed in the absorption and/or excitation spectra. [Rh,(PhNC),(dprn),] (PF6)2 was unique, exhibiting a relatively intense phosphorescence a t 10 500 cm-' a t room temperature in the solid state. Low-temperature phosphorescence lifetime data indicate an unusually small spin-orbit splitting of the 3Blu term into two levels separated by -7 cm-'. On the basis of the invariance of the splitting upon substitution of dam for dpm, we conclude that the electronic transition is u*(4d,z)u(5pz). These results are compared with those of other dimers studied recently and with those of related Rh (1) monomers. Registry No. [Rh2(t-BuNC)4(dpm)2](PF6)2, 80533-10-4; [Rh,(n-BuNC),(dprn),] (BPh4),, 80533-12-6; [Rh,(PhNC),(dpm),] (PF,),, 80533-14-8; [Rh,(n-B~NC)~(darn),](BPh~)~, 80533-16-0. ~~~~ ~ ~ (26) Strickler, S. J.; Berg, R. A.Abstract: Twelve isotopic species of fluoroethylene ozonide (vinyl fluoride ozonide or 3-fluoro-1,2,4-trioxolane) were synthesized including the parent and all eight possible singly substituted D, '*O, and "C species. The ground state microwave spectra of these were assigned as well as two excited vibrational states of the parent. The isotopic syntheses were consistent with the Criegee mechanism of ozonolysis. The dipole moment of the parent was found to be 2.317 (21) D, with principal axis components lwal = 1.456 (7), l~b l = 1.346 (34), IpCl = 1.199 (13). The ring conformation is a distorted twisted half-chair with the fluorine occupying an axial site, and with a long C-F bond length of 1.375 (5) A and short adjacent CF-0 bonds, both of 1.382 (10) A. The structure is rationalized in terms of the anomeric effect.The ozonolysis of alkenes in solvents has been known for over The ozonides produced in this reaction were first explained by the mechanism proposed by Criegee (Scheme 1 ) 3 3 4 and revised to include stereochemical effect^.^^^ Efforts to further 70 years.2

Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non‐steroidal anti‐inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student‐ and trainee‐led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre‐specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non‐selective cyclo‐oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.