An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine.

Abstract

Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6 ± 2.7% and 83.7 ± 1.7% (n=5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8 ± 3.4% (n=5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake of up to 49.0 ± 0.7% of the input dose was seen; in comparison, the uptake of [¹⁴C]phenylalanine under the same conditions was 55.9 ± 0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [¹⁴C]phenylalanine as the tracer, IC₅₀ values of 1.45 and 2.50 mM were obtained for Phe and I-Phe, respectively, and these values for [¹²⁵I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[(⁎)I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [¹⁴C]phenylalanine.

• Authors: Ganesan Vaidyanathan, Darryl McDougald, Linda Grasfeder, Michael R Zalutsky, Bennett Chin
• Journal: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine (Appl Radiat Isot) Vol. 69 Issue 10 Pg. 1401-6 (Oct 2011) ISSN: 1872-9800 [Electronic] England
• PMID: 21621415 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Carbon Radioisotopes
• Iodine Radioisotopes
• Radiopharmaceuticals
• Phenylalanine
• 4-iodophenylalanine

Topics

• Breast Neoplasms (metabolism)
• Carbon Radioisotopes (metabolism)
• Cell Line, Tumor
• Female
• Humans
• Iodine Radioisotopes (chemistry, metabolism)
• Isotope Labeling
• Phenylalanine (analogs & derivatives, chemical synthesis)
• Radiopharmaceuticals (chemical synthesis)