Timothy J. Tewson

Quantitative Imaging of Estrogen Receptor Expression in Breast Cancer with PET and 18F-Fluoroestradiol

The PET compound 18F-fluoroestradiol (18F-FES) has been developed and tested as an agent for the imaging of estrogen receptor (ER) expression in vivo. 18F-FES uptake has been shown to correlate with ER expression assayed in vitro by radioligand binding; however, immunohistochemistry (IHC) rather than radioligand binding is used most often to measure ER expression in clinical practice. We therefore compared 18F-FES uptake with ER expression assayed in vitro by IHC with both qualitative and semiquantitative measures. Methods: Seventeen patients with primary or metastatic breast cancer were studied with dynamic 18F-FES PET; cancer tissue samples, collected close to the time of imaging, were assayed for ER expression by IHC. For each tumor, partial-volume-corrected measures of 18F-FES uptake were compared with ER expression measured by 3 different ER scoring methods: qualitative scoring (0–3+), the Allred score (0–10), and a computerized IHC index. Results: There was excellent agreement (r = 0.99) between observers using IHC as well as the different methods of measuring ER content (P < 0.001). ER-negative tumors had 18F-FES partial-volume-corrected standardized uptake values of less than 1.0, whereas ER-positive tumors had values above 1.1. Correlation coefficients for the different measures of ER content and the different measures of 18F-FES uptake ranged from 0.57 to 0.73, with the best correlation being between the computerized IHC index and 18F-FES partial-volume-corrected standardized uptake values. Conclusion: Our results showed good agreement between 18F-FES PET and ER expression measured by IHC. 18F-FES imaging may be a useful tool for aiding in the assessment of ER status, especially in patients with multiple tumors or for tumors that are difficult to biopsy.

Iridium-Catalyzed Allylic Fluorination of Trichloroacetimidates

A rapid allylic fluorination method utilizing trichloroacetimidates in conjunction with an iridium catalyst has been developed. The reaction is conducted at room temperature under ambient air and relies on Et(3)N·3HF reagent to provide branched allylic fluorides with complete regioselectivity. This high-yielding reaction can be conducted on a multigram scale and shows considerable functional group tolerance. The use of [(18)F]KF·Kryptofix allowed (18)F(-) incorporation in 10 min.

Preparation of fluorine-18 aryl fluorides: piperidyl triazenes as a source of diazonium salts

Thermal decomposition of aryl diazonium salts of nonfluorinated acids in anhydrous media, generated by protonation of piperidyl triazenes, gives products resulting from reaction with added nucleophiles including high specific activity 18F-fluoride ions.

A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells

INTRODUCTION Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11CH3Ito[11C]-formaldehyde (11CH2O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11-14C]-(R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate (14CH2H4folate) by cancerous cell vs. normal cells from the same organ (Saeed M., Sheff D. and Kohen A. Novel positron emission tomography tracer distinguishes normal from cancerous cells. J Biol Chem 2011;286:33872-33878), pointing out 11CH2H4folate as a positron emission tomography (PET) tracer for cancer imaging. Herein we report the synthesis of 11CH2H4folate, which may serve as a potential PET tracer. METHODS In a remotely controlled module, methyl iodide (11CH3I) was bubbled into a reaction vial containing trimethylamine N-oxide in N,N-Dimethylformamide (DMF) and heated to 70°C for 2 min. Formaldehyde (11CH2O) formed after the completion of reaction was then mixed with a solution of freshly prepared tetrahydrofolate (H4folate) by using a fast chemoenzymatic approach to accomplish synthesis of 11CH2H4folate. Purification of the product was carried out by loading the crude reaction mixture on a SAX cartridge, washing with water to remove unbound impurities and finally eluting with a saline solution. RESULTS The synthesis and purification of 11CH2H4folate were completed within 5 min. High-performance liquid chromatography analysis of the product after SAX purification indicates that more than 90% of the radioactivity that was retained on the SAX cartridge was in 11CH2H4folate, with minor (<10%) radioactivity due to unreacted 11CH2O. CONCLUSION We present a fast (∼5 min) synthesis and purification of 11CH2H4folate as a potential PET tracer. The final product is received in physiologically compatible buffer (100 mM sodium phosphate, pH 7.0 containing 500 mM NaCl) and ready for use in vivo.

PET/CT with 18F-FLT Is Unlikely to Cause Significant Hepatorenal or Hematologic Toxicity

We would appreciate a statement from the authors on this matter. The discrepancy between the relatively low accuracy of perfusion SPECT plus low-dose CT and the high accuracy of V/Q SPECT plus CT in the study is considerable. It would be important to reanalyze the data to define the scintigraphic pattern responsible for the low specificity, 51%, when perfusion SPECT plus CT was used instead of V/Q SPECT plus CT. The information gained from this reanalysis would help us better understand the strengths and pitfalls of perfusion SPECT and help improve diagnostic confidence and accuracy.