What about PSMA for treatment follow up? Is there any evidence that treatment does not modify PSMA?
There are really few data on such topic, namely a couple of case reports (Schlenkoff 2016 and Hope 2017): both reported cases of modification of PSMA subsequent to treatment. It is absolutely not clear, however, if PSMA could be used for evaluating response to treatment: for sure it could be used in case of a PSMA documented lesion, then treated with good PSA response, that subsequently develops PSA increase.
I would like to know you experience and opinion on hormonal therapy impact on PSMA uptake?
Again there is not much data on such topic, and mostly preclinical studies. Murga 2014 indicates that inhibition of AR could increase PSMA expression and similar data were reported by Meller 2015 and Bahkt 2017; these data suggest that PSMA uptake could be increased by AR targeted therapies, with a relevant influence of timing. However there are almost no data in human, but the impression is that AR manipulation has influence on PSMA expression and thus uptake.
Leaving aside PET better resolution versus SPECT, what do you think about 99mTc-PSMA?
Form Vasko Kramer's point of view a very important development which will have a profound impact for several reasons:
Indication: First of all there is no doubt about the better resolution and sensitivity of PET compared to SPECT. Nevertheless this "optimal or high end performance" of PET may not be necessary in all cases and depends on the indication. For instance a patient with the indication of a PSMA-scan for stratification and evaluation for treatment with 177Lu-PSMA ERT might well receive a 99mTc-PSMA-scan as it shouldn't matter wether you find some more or less bone lesions. You would like to know if a patient has or not advanced metastatic disease, is a strong PSMA expresser and has or not bone marrow infiltration. Those questions should be possible to evaluate with either PSMA PET or SPECT.
Accessibility of PET / Costs: Maybe we also have to distinguish between different markets (or even clients or health care systems). Where PET/CT with 18F/68Ga-PSMA is broadly available and covered by insurance companies you should aim to perform the best diagnostic scan possible which would be PET. Especially for staging in primary PC or biochemically recurrence at low PSA values where sensitivity and resolution matters.
Nevertheless 99mTc-PSMA-SPECT/CT seems also to be superior compared to standard-of care (bone scan / MRI / CT) and may be a good option where PET is not accessible for any reason. Also the PET market today is still relatively small compared to traditional nuclear medicine and 99mTc-PSMA can be provided everywhere on the world without the need for a cyclotron.
Legal status: Up to my knowledge there is no approved PSMA-PET tracer in the market yet. 99mTc-labelled PSMA-1404 from Progenics is currently in phase III and might be the first FDA approved tracer and would most probably be covered my medicare and medicaid.
Since you have experience with both 68Ga and 18F-PSMA, have you experienced any difference in depicting small bone lesions with both targets? Would you say 68Ga-PSMA or 18F-PSMA do better or worse regarding bone lesions?
As far as Vasko Kramer understands 18F-PSMA detects more foci suspicious for bone lesions as 68Ga-PSMA which might indicate a higher sensitivity. Nevertheless we have not seen many studies which are able to confirm those lesions as tumor metastasis and 18F-PSMA (both FDCPyL & PSMA-1007) might have a lower specificity for detecting bone mets. But sure Rene and Eva con give you some mor details and insights about it...
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