Radiosynthesis and in vivo evaluation of [11C]MC80 for P-glycoprotein imaging

PET Radiotracers for Imaging P‐glycoprotein: The Challenge for Early Diagnosis in AD

“…In vivo studies performed in animal models with [ 11 C]MC80 demonstrated that although MC80 was not a suitable radiotracer for imaging of P-gp function at the BBB, it is a potential probe to image intestinal P-gp expression. [27] Among the biphenyl derivatives, the 11 C-radiolabeled form of MC113 was selected to perform in vivo studies. The aim of the present review is to illustrate the in vitro, the radiochemistry, and the in vivo PET studies of 11 C radiotracers previously described.…”

“…MC80 behaved as a transported substrate with an interacting profile similar to CsA but with an enhanced potency. [24,27] Chemistry and radiosynthesis [ 11 C]MC80 was synthesized by condensing the appropriate 2-naphtyl carboxylic acid with the isoquinoline moiety in the presence of carbonyldiimidazole and then by reducing the amide bond with lithium aluminum hydride . [24] The radiosynthesis of [ 11 C]MC80 was performed by 11 C labeling the phenolic precursor with [ 11 C]methyl iodide in the presence of sodium hydride as a base (Scheme 2).…”

“…The in vivo behavior of [ 11 C]MC80 was assessed in wild-type and mdr1a (À/À) mice. [27] In mdr1a (À/À) mice, [ 11 C]MC80 brain uptake was significantly increased compared to wild-type mice. In mdr1a (À/À) mice, a slower distribution of [ 11 C]MC80 to peripheral organs and a decreased retention of the tracer in the excretory organs was observed.…”

11C‐ and 18F‐Labeled Radioligands for P‐Glycoprotein Imaging by Positron Emission Tomography

“…Given that ABC transporters are flexible proteins that bind to several distinct molecules, it is a challenge to find specific radiolabeled compounds that are capable of measuring a single transporter subtype in vivo. Colabufo and colleagues tested several P‐gp modulators that behave as substrates, inhibitors, or even inducers depending on slight changes in their molecular structures . In a preclinical study, two new PET probes were developed: a P‐gp inhibitor [ 11 C]MC18 ([ 11 C]‐ 3 ), which showed specific binding in the brain and several peripheral target organs and is, therefore, useful to assess P‐gp expression, and [ 11 C]MC266 ([ 11 C]‐ 4 ), a P‐gp substrate with higher baseline uptake than [ 11 C]‐ 1 suitable for measurement of P‐gp activity .…”

“…Colabufo and colleagues tested several P-gp modulators that behave as substrates, inhibitors, or even inducers depending on slight changes in their molecular structures. [19][20][21][22] In ap reclinical study,t wo new PET probesw ere developed:aP-gp inhibitor [ 11 C]MC18 ([ 11 C]-3), which showeds pecific binding in the brain and several peripheral target organs and is, therefore, usefult oa ssess P-gp expression,a nd [ 11 C]MC266( [ 11 C]-4), aP -gp substrate with higher baselineu ptake than [ 11 C]-1 suitable for measurement of P-gp activity. [18] In ar ecent PET study,t he new compound [ 11 C]MC113w as tested in mice.…”