HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lampiri, I. Articles by Goldsmith, S. PubMed Articles by Lampiri, I. Articles by Goldsmith, S.

4-(n-[¹¹C]methyl)Amino benzhydrazide (MM-ABAH): A new PET tracer to image atherosclerosis

¹ Radiology, Citigroup Biomedical Imaging Center (CBIC), Weill Cornell Medical College, Cornell University, New York, New York

1289

Objectives: The enzyme myeloperoxidase (MPO), known to be present in atherosclerotic lesions (ASL) and is involved in the oxidation of low density lipoprotein (LDL). It has also been reported that MPO in ASL is derived from macrophages. MPO would be a valid target for imaging of vulnerable ASL in vivo. Benzoic acid hydrazides such as 4-aminobenzoic acid hydrazide (ABAH) have been identified as preferred inhibitors of MPO. Its binding leads to irreversible inactivation of the enzyme by a suicide substrate mechanism. We report here the synthesis of ¹¹C labeled analog of ABAH as a PET tracer for for noninvasive imaging of vulnerable ASL.

Methods: [¹¹C]CO₂ was produced using an EBCO-TR19 cyclotron by proton bombardment of a target filled with nitrogen containing 0.5% oxygen. [¹¹C]methyliodide was made using GE MicroLab or TracerLab FXc. 1-3 mg of ABAH in 0.3 mL DMF was incubated with [¹¹C]methyliodide for 3 min at 80^oC. The ¹¹C labeled products were separated by HPLC. Methylation of ABAH may result in analogs of ABAH; monomethyl ABAH (MM-ABAH) and dimethyl ABAH (DM-ABAH). In order to identify the labeled products we have initially synthesized MM-ABAH and established the identity by NMR and HPLC.

Results: The HPLC analysis of ¹¹C incubation mixure clearly identified 3 radioactive peaks with retention times (RT) of 1.8, 3.7 (MM-ABAH) and 15 min (methyl iodide). We synthesized MM-ABAH a radiolabeling yield of 12-15% with a radiochemically purity of >98%. The specific activity of the final product was 500 mCi/µmoles @EOB.

Conclusions: We successfully prepared [¹¹C]MM-ABAH optimal for biological testing and in vivo studies in an atherosclerosis animal model. Optimization of labeling procedure to improve yields is in progress.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lampiri, I. Articles by Goldsmith, S. PubMed Articles by Lampiri, I. Articles by Goldsmith, S.