title: Preparation and preliminary evaluation of 4-[211At]astato-N-piperidinoethyl benzamide.
abstract: The potential therapeutic agent, 4-[211At]astato-N-piperidinoethyl benzamide (4-APAB) was synthesized via a halodestannylation reaction. Radiochemical yields were 69% for a 5 min reaction and reached 74% by 25 min, whereas 82% radiochemical yields were obtained under similar reaction conditions for radioiodination. A simplified procedure was adopted for the purification of the target compound. In vitro binding of 4-APAB to SK-MEL 28 melanoma and D247 glioma cell lines was 20.7 +/- 1.3% and 12.2 +/- 1.3%, respectively. In comparison, binding of 4-[131I]iodo-N-piperidinoethyl benzamide (4-IPAB) to SK-Mel 28 cells was 13.9 +/- 1.9%. Paired label biodistribution studies were performed in normal Balb/c mice using 4-IPAB and 4-APAB. Thyroid uptake at 1, 2, and 6 h was significantly higher for 4-APAB. Differences in liver accumulation between the two compounds were small but statistically significant at most time points. A higher accumulation of 211At compared with 131I was observed in lungs and spleen at all time points studied. These results indicate that 4-APAB is not stable in vivo, suggesting the need for a better sigma receptor ligand for use in 211At.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Garg
authors.forename: C S
authors.initials: CS
authors.lastname: John
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D001246:Astatine / Q000378:metabolism / Q000493:pharmacokinetics; D001549:Benzamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005910:Glioma; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism; D008545:Melanoma; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D013154:Spleen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C095745:4-astato-N-piperidinoethylbenzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D007457:Iodine Radioisotopes; D010880:Piperidines; C084662:4-iodo-N-piperidinoethylbenzamide; D001246:Astatine