Synthesis of [¹⁸F]Fluoroalanine and [¹⁸F]Fluorotamoxifen for Imaging Breast Tumors

Abstract

To develop ligands for imaging breast tumors, [18F]fluoro analogue of tamoxifen and [18F]fluoroalanine were radiosynthesized. In vivo biodistribution studies were performed in mammary tumor-bearing rats. In studies on the biodistribution of an [18F]fluoro analogue of tamoxifen, tumor uptake decreased when rats were pretreated with diethylstilbestrol (DES), suggesting that tracer uptake in tumors was receptor-mediated. An estrogen receptor assay indicated that tumors have a receptor density of 7.5 fmol/mg protein. Studies of the distribution of [18F]fluoroalanine in tissue showed that the tumor-to-tissue ratio increases as a function of time. Positron emission tomography (PET) images of tumor-bearing rats demonstrated that tumors can be visualized 1 h after rats are injected with an [18F]fluoro analogue of tamoxifen. PET imaging of pigs after injection of 10 mCi of [18F]fluoro analogue of tamoxifen showed uterine uptake that could be blocked by DES (50 mg). The findings suggest that both radiotracers are useful for imaging breast tumors.

Imaging in breast cancer: Single-photon computed tomography and positron-emission tomography

“…However, few studies compared these radiopharmaceuticals with other diagnostic methods. Those radiolabeled amino acids studied in breast cancer include L-[ 18 F]α-methyltyrosine [96], [ 11 C]methionine [96,97], [ 18 F]fluoroalanine [98] and [ 11 C]tyrosine [99]. During chemotherapy courses, the uptake of [ 11 C]methionine from metastases decreased in cases of stable or responsive disease and increased in cases of progressive disease [97].…”

“…This led the authors to conclude that metabolic changes in radiolabeled amino acid incorporation measured by PET preceded the clinical response. Studies of the distribution of [ 18 F]fluoroalanine in tissue showed that the tumor : tissue ratio increased as a function of time, suggesting that this tracer could be of interest in detecting breast cancer [98]. [ 11 C]Tyrosine seemed to visualize malignant breast tumors as effectively as 18 F-FDG, but the visual contrast was better with 18 F-FDG.…”

Synthesis, Biodistribution, and Estrogen Receptor Scintigraphy of Indium-111—Diethylenetriaminepentaacetic Acid–Tamoxifen Analogue

“…16,17 Conversely, placing an iodine atom on the aromatic ring reportedly lowers the affinity. 23 Both 18 F-and 131 I-labeled tamoxifen analogues show high uptake by liver, 24 which interferes with the interpretation and localization of breast tumors. Other radiolabeled steroids also show higher uptake by liver and lung.…”

Methods for 11C‐ and 18F‐labelling of amino acids and derivatives for positron emission tomography imaging

“…The synthesis of [ 18 F]fluoroalanine (2‐amino‐3‐[ 18 F]fluoropropionic acid, 13 ) by a substitution reaction of a protected tosylserine precursor led to radiochemical yields of less than 1%, why it found no clinical application. Further examples in this series are the synthesis of 2‐amino‐4‐[ 18 F]fluoromethylsulfanylbutyric acid ([ 18 F]fluoromethionine, 14 ) and 4‐[ 18 F]fluoro‐ l ‐glutamic acid (BAY 85–8050, 15 ) …”