Journal of Labelled Compounds and Radiopharmaceuticals

Zessin, J.; Steinbach, J.; Johannsen, B.

doi: 10.1002/(SICI)1099-1344(199908)42:8<725::AID-JLCR231>3.0.CO;2-8pmid: N/A

The synthesis of the new and highly reactive 11C‐precursor triphenylarsonium (11C)methylide 1 and its conversion into (2‐11C)indole 6 is described. (11C)Methyl‐triphenylarsonium iodide 4 was prepared by quaternization of triphenylarsine 2 with (11C)methyl iodide 3 in a THF/DMSO mixture or ethanol. Starting from 3, (11C)methyl‐triphenylarsonium iodide 4 was obtained in a decay‐corrected radiochemical yield of 55%–64% depending on the reaction solvent. The arsonium ylide 1 was prepared in situ by treatment of 4 with butyllithium. Conversion of 1 with o‐aminobenzaldehyde 5 in THF/DMSO mixtures yielded (2‐11C)indole 6 in radiochemical yields of 23–27% (decay‐corrected, in relation to 3). Preparation of 6 was completed after 15–20 min (starting from 3). The specific radioactivity of 6 was about 37 GBq/μmol (1 Ci/μmol, related to EOB). Copyright © 1999 John Wiley & Sons, Ltd.

Hjelstuen, O. K.; By, B. C.; Cleynhens, B.; Ormstad, H. M.; Roald, T. E.; Tønnesen, H. H.; Bremer, P. O.; Verbruggen, A. M.

doi: 10.1002/(SICI)1099-1344(199908)42:8<737::AID-JLCR233>3.0.CO;2-Ypmid: N/A

Antisense oligodeoxynucleotides (ODNs) conjugated to a suitable bifunctional chelating agent and labelled with a suitable radionuclide could become useful in the diagnosis and differentiation of cancers. Radiolabelled natural DNA with phosphodiester (PO) backbone is a candidate for use in imaging, while phosphorothioate (PS) ODNs already are proving their efficacy in antisense therapy. In this study, two PO and two PS ODNs have been conjugated with the N2SO chelator MAG2 in a procedure designed to make a N3S tetraligand which forms stable complexes with technetium‐99m. Depending on the S‐protecting group used and reaction conditions employed, labelling yields of more than 90% can routinely be obtained. The 99mTc‐MAG2‐ODNs are stable in solution, even in the presence of a 30‐fold excess of cysteine. However, at higher concentrations of cysteine and in foetal calf serum they are not stable. In vivo in mice, the PO 99mTc‐MAG2‐ODNs are degraded more than 50% in 5 min, while the PS analogues remain intact. The PS and PO 99mTc‐MAG2‐ODNs are distributed in a similar fashion in normal mice, except for a higher liver retention of the PO 99mTc‐MAG2‐ODNs at 60 min. Copyright © 1999 John Wiley & Sons, Ltd.

Spang, J. E.; Patt, J. T.; Westera, G.; Schubiger, P. A.

doi: 10.1002/(SICI)1099-1344(199908)42:8<761::AID-JLCR234>3.0.CO;2-Spmid: N/A

The two epibatidine (EPB) analogues dechloro‐epibatidine (DC1‐EPB) and 2PABH were synthesised via a two step reaction starting from N‐methoxycarbonyl‐7‐ azabicyclo(2.2.1)heptene. The radiochemical syntheses of (11C)N‐methylated derivatives was performed using the classical methylating agent (11C)CH3I in acetonitrile. The radiochemical yield ranged from 5 to 10% (decay corrected from (11C)CH3I) and was fully sufficient for small animal experiments. High specific activities in the range of 140 to 360 GBq/μmol at EOS (end of synthesis) were obtained. The radiosynthesis, semipreparative HPLC, formulation and quality control were completed in an average time of 35 min. Copyright © 1999 John Wiley & Sons, Ltd.

Demin, P. M.; Vasiljeva, L. L.; Kochev, D. M.; Pivnitsky, K. K.; Pace‐Asciak, C. R.

doi: 10.1002/(SICI)1099-1344(199908)42:8<773::AID-JLCR237>3.0.CO;2-Epmid: N/A

Methyl (8S)‐(20‐3H)‐8,20‐dihydroxy‐11,12‐epoxy‐5Z,9E,14Z‐eicosatrienoate ((8S)‐(20‐3H)‐20‐hydroxy‐HxA3 methyl ester), a radioactive analog of the HxA3 metabolite was prepared. The synthesis of the 20‐hydroxy analog of HxA3 methyl ester was performed by the reduction of the corresponding 20‐aldehydro‐HxA3 with sodium (3H)‐borohydride. The purified (20‐3H)‐20‐hydroxy‐HxA3 methyl ester had a specific activity of 2.5–2.7 Ci/mmol. Copyright © 1999 John Wiley & Sons, Ltd.

Dejesus, Onofre T.; Nickles, R. Jerome; Murali, Dhanabalan

doi: 10.1002/(SICI)1099-1344(199908)42:8<781::AID-JLCR238>3.0.CO;2-Apmid: N/A

(18F)Fluoro‐o‐tyrosines (FOT) were prepared by the direct reaction of (18F)acetylhypofluorite with L‐o‐tyrosine. Two isomers were formed in this reaction, 3‐FOT and 5‐FOT, with unoptimized decay‐corrected isolated radiochemical yields of about 11% and 8%, respectively. Results of preliminary in vitro evaluation found 5‐FOT to be the more promising isomer and suggest further evaluation of this compound as aromatic amino acid decarboxylase (AAAD) PET tracer should be undertaken. Copyright © 1999 John Wiley & Sons, Ltd.

Liu, Shengquan; Berlin, K. Darrell; Simms‐Kelley, Melissa D.; Nelson, Eldon C.; Benbrook, Doris M.

doi: 10.1002/(SICI)1099-1344(199908)42:8<789::AID-JLCR239>3.0.CO;2-#pmid: N/A

Heteroarotinoids may be useful in the treatment of skin disorders and a wide variety of cancers. A synthesis of the C‐14 labelled heteroarotinoid, (E)‐4‐(2‐(3,4‐dihydro‐4,4‐dimethyl‐2H‐1‐benzopyran‐6‐y1)‐1‐propenyl)benzoic acid‐11‐(14C) (*1) is described via a multistep procedure similar to that used to obtain the unlabelled compound 2. The latter has shown good activity in several assays compared to the standard trans‐retinoic acid (3). Reduction of the carbonyl group in 4,4‐dimethylchroman‐6‐y1 methyl ketone‐(carbonyl‐14C) (*5) with LiA1H4 gave alcohol *6. Phosphorylation with triphenyl‐phospine hydrobromide in methanol led to the corresponding phosphonium salt *7. Addition of n‐butyllithium to *7 in ether at −78°C generated the Wittig reagent in situ and to this was added ethyl 4‐formylbenzoate. Workup and chromatography afforded E‐ester *8 and Z‐ester *9 which were both hydrolyzed to labelled *1 . Labelled *1 was identical to unlabelled 2 in terms of spectral data and melting point. The specific activity of *1 was determined to be 57.2 μCi/mg. Copyright © 1999 John Wiley & Sons, Ltd.

Shu, A. Y. L.; Saunders, D.; Levinson, S. H.; Landvatter, S. W.; Mahoney, A.; Senderoff, S. G.; Mack, J. F.; Heys, J. R.

doi: 10.1002/(SICI)1099-1344(199908)42:8<797::AID-JLCR240>3.0.CO;2-Opmid: N/A

A variety of complex compounds have been labeled with tritium gas by catalytic exchange in the presence of catalyst precursors ((cod)Ir(dppe))BF4 or ((cod)Ir(py)(PCy3))BF4. In most cases, predictable regioselectivity and high specific activities are achieved. These results are compared in some cases to the results of labeling related compounds with ((cod)Ir(PPh3)2)BF4. Prereduction of the catalyst precursors in situ with hydrogen allows the use of smaller quantities of tritium gas and reduces the amount of radioactive waste. Two or more compounds can be labeled simultaneously as mixtures then separated in the HPLC purification step to increase compound throughput. Copyright © 1999 John Wiley & Sons, Ltd.

Adam, Michael J.

doi: 10.1002/(SICI)1099-1344(199908)42:8<809::AID-JLCR241>3.0.CO;2-8pmid: N/A

This paper describes the synthesis and preliminary in‐vivo study of a new FDG analog, 2‐deoxy‐2,2‐(18F)difluoro‐glucose (DFDG) for use as a potential imaging agent for PET. DFDG was prepared by the reaction of 18F‐acetyl hypofluorite on 3,4,6‐tri‐O‐acetyl‐2‐fluoro‐D‐glucal followed by acid deprotection to give the final product in 27% decay corrected radiochemical yield. Biodistribution in mice showed rapid uptake in the heart (10% dose/gram) which remained relatively constant out to two hours. The brain uptake at 2 hours was 1.6% dose per gram. There was rapid clearance of activity from the blood after injection. Brain images in a Rhesus monkey showed a similar distribution when compared to FDG but with significantly more uptake in surrounding muscle. Copyright © 1999 John Wiley & Sons, Ltd.