Choline

10.2.1 Radiopharmaceuticals

• [¹⁸F]Fluorocholine (FCH)
• [¹¹C]Choline

10.2.2 Uptake mechanism/biology of the tracer

Choline plays an essential role in the biosynthesis of phospholipids which are the main component of cell membranes, both of normal and cancer cells. The increased metabolic demands of neoplastic cells determine an increase of the Choline request resulting in a hyperactivity of the enzymes (choline-kinase) involved in its metabolic pathway. The rapid tumour growth in fact is characterized by an increase of the phospholipids, especially phosphatidylcholine, which are the fundamental constituents of the membrane, being also able to influence the cell proliferation and cell differentiation [179,180].

10.2.3 Indications: Prostate cancer

PET/CT with Choline is a valuable imaging tool for visualizing prostate cancer. It plays an important role in imaging prostate cancer patients in the staging and in the restaging phases [181–183]. However, the main clinical indication of PET labelled Choline in prostate cancer is the restaging after primary treatment when a biochemical recurrence occurs [184–187].

10.2.4 Other indications in Oncology

Choline has been successfully used to characterize primary Hepato Cellular Carcinoma (HCC) or metastatic lesions from HCC. In the characterization of suspected HCC, the combined use [¹¹C]Choline and [¹⁸F]FDG may increase the sensitivity of PET/CT up to 93% [188]. The use of Choline in HCC may have a significant impact on clinical management. The information provided by [¹¹C]Choline PET/CT lead  to a management change in 30% of  73 patients with HCC  referred for staging (42 patients) or suspect of relapse (31 patients) [189].

Choline has been used to study suspect recurrent brain tumours where MRI findings are inconclusive  or to guide Radiation Treatment planning [190].

10.2.5 Contra-indications

Pregnancy.

10.2.6 Clinical performances

Several studies are now available on the role of PET/CT with Choline in the context of prostate cancer. In particular, for the identification of the primary tumour the role is still controversial because of its low specificity. The method is not able to accurately distinguish between neoplastic tissue, benign pathological tissue, and normal tissue. As for primary staging, its role for the identification of lymph node metastasis has not been clearly demonstrated due to its limited spatial resolution that can cause a failure in the detection of micro metastases. However, in high-risk prostate cancer patients, Choline PET/CT can provide valuable information for the detection of both lymph node and bone metastases [181]. The field where Choline PET/CT method does have a clinically established role is the restaging, when the patient radically treated for prostate cancer presents an increased PSA serum value. Several literature studies have shown that Choline PET/CT can accurately highlight the prostatic disease recurrence, in particular at lymph nodal and skeletal sites. In a large single centre study performed in 3,203 patients showing biochemical recurrence (BCR) ¹¹C-choline has been able to detect recurrence  in 54.8 % of the patients and in  29.4 % of the scans, at least one distant finding was observed [183].

This evidence supports the use of PET/CT with Choline as a guide for planning personalized treatment options. In particular, it has been described that Choline PET/CT is a valuable tool for planning and monitoring therapy in lymph node recurrences after primary treatment. It been documented as the radiant high-dose treatment, guided by Choline PET/CT is well tolerated and associated with a high response rate [191].

Finally, [¹¹C]choline has shown a significant prognostic value in patients with Biochemical recurrence after primary treatment [192,193].

10.2.7 Activities to administer

The suggested activities to administer

• [¹⁸F]FCH: 4 MBq/kg ; 50 – 400 MBq
• [¹¹C]choline: 400 – 600 MBq

10.2.8 Dosimetry

The effective dose for [¹⁸F]FCH is 20 µSv/MBq [3]. The organ with the highest absorbed dose is the kidneys: 97 mGy/MBq

The effective dose in an adult of 70kg for [¹¹C]Choline is 4.4 µSv/MBq which is equivalent to 2.0 mSv from 460 MBq [163]. The organ with the highest absorbed dose is the pancreas: 29 mGy/MBq

The range in effective dose for [¹⁸F]FCH is: 1 – 8 mSv per procedure.

The range in effective dose for [¹¹C]Choline is: 2.6 – 4.0 mSv per procedure. The radiation exposure related to a CT scan carried out as part of a choline PET/CT study depends on the intended use of the CT study and may differ from patient to patient.

Caveat

:“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

10.2.9 Interpretation criteria / major pitfalls

For a proper interpretation of Choline PET/CT images, it is necessary:

• Establish proper contrast of grayscale and/or colour;
• Know the spatial resolution of the PET scanner;
• Check the data regarding the administration and the acquisition parameters (activity administered, the time between administration and acquisition, etc.);
• On the MIP image it is advisable to set the colour scale and/or of grey until the voxel in the liver reaches the maximum of counts (upper level) without subtracting the bottom (lower level = 0).

To interpret the images, consider:

• The physiological distribution of Choline-intense uptake: major and minor salivary glands, kidney, pancreas, bladder, and ureters;
• The possible locations of physiological and "para-physiological" uptake of Choline of varying amounts: gastrointestinal tract, bone marrow, mediastinal lymph nodes;
• The accumulation of Choline in correspondence of inflammatory processes;
• The Choline accumulation in correspondence of neoplastic lesions;
• The acquisition protocol used (i.e., Dynamic acquisition);
• The anatomical location of Choline accumulations;
• Knowledge of the causes that can lead to false positive and false negative results.

False positives:

• Physiological uptake sites of Choline tracer;
• Inflammatory processes (i.e., Mediastinal lymph nodes, sarcoidosis);
• Benign tumours (i.e., Meningioma);
• Hyperplasia (i.e., Parathyroid adenoma or adrenal adenoma);
• Drug therapies (i.e., skeletal remodelling).

False negatives:

• Small dimension lesions;
• Tumours located within the physiological uptake of metabolic tracer;
• Skeletal metastases with high component blast;
• Drug therapies that may interfere with the accumulation of Choline;
• Recent therapy (i.e. chemotherapy or radiotherapy);

Artefacts:

• By attenuation;
• Non-alignment of CT with PET;
• By truncation;
• From dense materials;
• Motion;
• Related to instrumentation;
• Related to the processing procedures.

10.2.10 Patient preparation

Pre-injection phase:

• The patient should be placed in rest conditions - removal of metal objects;
• Fasting condition;
• In the case of PET/CT with contrast medium is recommended the cannula needle for the injection of the contrast medium - sedation in case of patients anxious or claustrophobic.

10.2.11 Methods

Total-body acquisition extending from the skull or sub-orbital regions to the feet or the mid-thighs.

PET examination is routinely evaluated by qualitative analysis: assessing the uptake of Choline between a diseased and a reference area (i.e., surrounding anatomical structures). In this case, the uptake of the entity can be quantified as mild, moderate or intense than the reference zone.