Confirming the pharmacological interaction between colchicine and 18F-choline PET

We recently encountered a previously unknown pharmacological interaction in a
patient, involving the apparent complete blocking of choline metabolism by
colchicine (used to suppress inflammation in gout). This interaction resulted
in a dramatically altered biodistribution of radiolabeled 18F-methyl-choline on
positron emission tomography (FCH-PET), and prevented adequate molecular
imaging for staging of prostate cancer in this patient. We identified
colchicine as the likely cause of the distorted FCH-PET, as the biodistribution
of FCH returned to normal after withdrawal of colchicine.

This interaction is considered clinically relevant, as it may result in
suboptimal diagnosis and staging of cancer, and we now advise to withdraw
colchicine prior to FCH-PET. However, the effect was demonstrated in only one
patient, and it may have been patient-specific or influenced by other unknown
factors. The current study aims to confirm the hypothesis that there is an
interaction between colchicine and the choline pathway as seen with FCH-PET.

Colchicine may not be the only drug interfering with choline metabolism and
FCH-PET. Other anti-mitotic drugs that target intracellular tubulin and result
in catabolic phosphatidylcholine metabolism, including e.g. docetaxel,
paclitaxel and vincristine, may yield the same effects. It is imperative that
we understand interactions for this group of drugs, in order to guide imaging
and avoid diagnostic and treatment errors. In the present study we focus on the
interaction between colchicine and FCH-PET. If this interaction is confirmed,
we will continue with a second study focussed on the interactions between other
tubulin targeting drugs and FCH-PET.

Confirm the interaction between colchicine and the choline pathway as seen with
FCH-PET.

A mono-centre interventional study, comparing the biodistribution of FCH in the
absence and presence of colchicine. Patients receiving routine FCH-PET on
clinical indication will be asked to undergo an additional FCH-PET scan after
premedication with 1 mg colchicine per os.

After the routine FCH-PET scan, an addition FCH-PET will be performed with
premedication 1 mg colchicine per os.

Colchicine 1 mg per os is the normal start of treatment for an exacerbation of
gout. No side effects or risks are known or expected from a single
administration. Patients with pre-existent bone marrow or kidney disease will
be excluded. FCH-PET(/CT) is a routine clinical imaging modality, with a
duration of maximum 1 hour and a radiation burden of ~8 mSv, similar to other
routine diagnostic procedures, without known or expected side effects, and
without known or expected risks (especially in the evaluated group of patients
with recurrent or metastasized cancer). The results of this study will have no
impact on clinical decision-making or treatment for participating patients.