Variability of quantitative Ga68-PSMA PET: a test-retest pilot study

The optimal treatment for metastatic prostate cancer depends on characteristics
of the tumour and of the patient, and may consist of multiple modalities
including hormone, chemo, radiation, and radionuclide therapy. The options for
systemic treatment of bone metastases have recently been expanded with the
radionuclide Radium-223, providing improved survival with low toxicity. The
effectiveness of any treatment should be monitored, in order to refrain from
ineffective therapy, unneeded costs and avoidable side effects.

Treatment monitoring in patients with metastatic prostate cancer is difficult,
especially with respect to the response of bone metastases. Nor blood testing
(PSA), nor radiological imaging (CT or MRI) is sufficiently reliable. Also
skeletal scintigraphy is unable to discriminate response and signal flare due
to bone repair. Metabolic imaging with FDG-PET has limited sensitivity for
prostate cancer and is potentially compromised by inflammation after
irradiation. Functional metabolic imaging with other radiolabeled ligands, such
as 68Ga-PSMA and positron emission tomography (PSMA-PET) is promising, however.

It is known that uptake measurements of radiolabeled tracers with PET in vivo
suffer from many inaccuracies, as demonstrated by experience with FDG, and that
this requires evaluation and standardisation prior to application as response
parameter. This probably applies equally to PSMA-PET. Before quantification of
PSMA uptake can be used as a biological parameter to identify response to
treatment, and before we can design sufficiently powered response evaluation
studies, we need to know the characteristics of the measurement technique. An
important factor that is currently unknown is the normal day-to-day variability
in tumour and normal tissues. This signal variability is currently unknown and
will be evaluated in this pilot study in a sufficiently large cohort of
patients in whom recurrent prostate cancer is suspected.

Q.Clear. With respect to the technical imaging parameters, image reconstruction
could be of special interest due to better signal-to-noise ratios (SNRs) that
are claimed using a Bayesian penalized reconstruction algorithm called Q.Clear,
especially for lesions smaller than 3 cc. It is tempting to speculate that
these claimed better SNRs translate into higher absolute values and less total
variability of quantitative PSMA uptake in these smaller lesions.

The objectives of the study are twofold:
1) Determination of the absolute values and variability of PSMA uptake in
tumour tissue and in normal tissues, including muscles, liver, spleen, bone
marrow
2) Determination of the absolute values and variability in PSMA uptake in
tumour tissue and in normal tissues, with or without Q.Clear.Tumour lesions
will be stratified by lesion size.

Single center prospective observational study, in which the test-retest
variation of PSMA uptake in tissues (both tumour and normal) will be
determined. Tumour lesions will be divided between small (< 3 cc) and non small
(>= 3 cc) lesions. Two data sets will be constructed, one with Q.Clear and one
without. The timeframe for the study is two to three years, depending on how
many patients are willing to participate. If one out of three is willing to
participate it will be three years. The duration can be reduced to two years if
one out of two patients can be included.

Patients will not have any benefit from participating in this study, and they
will have very limited additional risk. The repeated PSMA PET scan is not
expected to provide any clinically relevant new information, it will not be
reviewed or reported as such, and it will not have impact on clinical diagnosis
or treatment decisions. Patient burden of participation is generated by one
additional visit to the hospital of at maximum one hour, one vena punction with
one tracer administration, and a total additional radiation burden of ~6 mSv.
This radiation burden is in the range of standard diagnostic tools, and is not
considered an additional clinically relevant risk in relation to their
biochemically recurrent prostate cancer with macroscopic disease.