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The following message was posted to: PharmPK
I have done in the past tissue distribution studies with iodinated
proteins and peptides and found that, at least in some cases, the data
are consistent with the distribution of iodide (which is well studied
in the literature). My goal would be to prevent studying iodide again.
Has anyone out there done some sort of preliminary in vitro experiment
that has proven predictive in estimating the stability of the iodide
label in vivo? Obviously one purifies the peptide so there is no
residual iodide in it, and one can give cold iodide to minimize
radiolabeled iodide uptake but I would prefer to avoid the experiment
altogether, (or at least go with a different label) rather than waste
time and money doing yet another iodide distribution study.
A second question concerns the dosimetry calculations for human
radiolabeled studies. In the past I have done this from traditional
excision TD studies, where one can estimate the radioactivity AUC from
the tissues, scale up to human organs etc. My question is, how are
folks doing these calculations from QWBA data? QWBA gives tissue
concentrations just as excision studies do, so I suppose the same
approach can be taken. Is there another approach? QWBA is usually done
with fewer timepoints than tradtional excision studies and thus the PK
must be inherently less reliable. Just to head off a reply, I know
these studies can be done by accelerator MS with much less label, but
that's not the issue here.
I guess we could raise the more general question. How does the
collected wisdom of the group feel about WBA vs. excision? Certainly
one gets data from WBA that is not available from excision studies,
such as distribution of label within the tissues, and in small organs
that might not be collected (or may not be collected free from
surrounding tissue). Another advantage of WBA, and I don't mean this
disparagingly, is the pretty pictures. Showmanship is important if we
are to have our ideas listened to, especially by the less technical
members of our organizations. But the strengths of WBA are also
drawbacks. The ability to measure specific areas of organs means one
does not get the concentration averaged over the whole organ, only the
parts appearing in the slice. Also in my experience, tissue
concentrations measured by QWBA do not agree well with those determined
in excision studies. Grinding and burning are very reliable analytical
techniques, and I think the estimations of concentrations from
standards embedded in the slices less so. The matrix effects on
counting CO2 are minimal (smile), and one cannot fortify whole tissue
for every tissue and embed them with the slices. It seems that blood
or plasma are used because of convienience, and they may or may not be
relvant for a given tissue. I guess my take on the issue is that both
techniques are valuable, and I try to both when I do these studies, but
if I only get one, I think I go with excision.
Dale Sharp
Back to the Top
The following message was posted to: PharmPK
I have done in the past tissue distribution studies with iodinated
proteins and peptides and found that, at least in some cases, the data
are consistent with the distribution of iodide (which is well studied
in the literature). My goal would be to prevent studying iodide again.
Has anyone out there done some sort of preliminary in vitro experiment
that has proven predictive in estimating the stability of the iodide
label in vivo? Obviously one purifies the peptide so there is no
residual iodide in it, and one can give cold iodide to minimize
radiolabeled iodide uptake but I would prefer to avoid the experiment
altogether, (or at least go with a different label) rather than waste
time and money doing yet another iodide distribution study.
A second question concerns the dosimetry calculations for human
radiolabeled studies. In the past I have done this from traditional
excision TD studies, where one can estimate the radioactivity AUC from
the tissues, scale up to human organs etc. My question is, how are
folks doing these calculations from QWBA data? QWBA gives tissue
concentrations just as excision studies do, so I suppose the same
approach can be taken. Is there another approach? QWBA is usually done
with fewer timepoints than tradtional excision studies and thus the PK
must be inherently less reliable. Just to head off a reply, I know
these studies can be done by accelerator MS with much less label, but
that's not the issue here.
I guess we could raise the more general question. How does the
collected wisdom of the group feel about WBA vs. excision? Certainly
one gets data from WBA that is not available from excision studies,
such as distribution of label within the tissues, and in small organs
that might not be collected (or may not be collected free from
surrounding tissue). Another advantage of WBA, and I don't mean this
disparagingly, is the pretty pictures. Showmanship is important if we
are to have our ideas listened to, especially by the less technical
members of our organizations. But the strengths of WBA are also
drawbacks. The ability to measure specific areas of organs means one
does not get the concentration averaged over the whole organ, only the
parts appearing in the slice. Also in my experience, tissue
concentrations measured by QWBA do not agree well with those determined
in excision studies. Grinding and burning are very reliable analytical
techniques, and I think the estimations of concentrations from
standards embedded in the slices less so. The matrix effects on
counting CO2 are minimal (smile), and one cannot fortify whole tissue
for every tissue and embed them with the slices. It seems that blood
or plasma are used because of convienience, and they may or may not be
relvant for a given tissue. I guess my take on the issue is that both
techniques are valuable, and I try to both when I do these studies, but
if I only get one, I think I go with excision.
Dale Sharp
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)