*3.1. 18F-Choline and 11C-Choline*

Choline is a component of phosphatidylcholine and, as such, functions as a substrate for cell membrane biosynthesis. The uptake of radiolabeled choline is increased in proliferating cells because it is involved in membrane metabolism and growth. Choline PET imaging has been traditionally used in the diagnostics of prostate cancer.

The first report of 11C-choline uptake in myeloma lesions was an incidental finding of a solitary plasmacytoma in a patient being re-staged for prostate cancer [35]. Based on this finding, a comparison study of 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement was performed by the Bologna group in a heterogeneous group of 10 MM patients (4 patients at completion of initial therapy, 2 during follow-up and 4 at disease relapse). In 2/10 patients with suspicion of disease relapse, both the 11C-Choline and 18F-FDG PET/CT scans were positive and identified the same number and sites of bone lesions. In 4/10 patients, both techniques were positive, but 11C-choline identified a nonsignificant higher number of lesions than 18F-FDG. Finally, 4 patients were negative with both tracers, a finding consistent with clinical, laboratory and radiological data indicating a CR at the time of imaging [36]. Almost ten years later, another pilot study on choline PET was published on a larger MM patient cohort. Twenty-one patients with suspected progressive or relapsing MM were studied with 18F-choline and 18F-FDG PET/CT. No myeloma lesions were detected in two cases, while uncountable foci were observed in four patients. In the rest, 15 patients with countable bone foci, 18F-choline PET/CT depicted

a significantly higher number of lesions than 18F-FDG PET/CT [37]. Further, the performance of 18F-choline and 18F-FDG PET/CT in the detection of skeletal involvement was compared in a case series of five MM patients in a pairwise fashion. Skeletal lesions were detected in all five 18F-choline PET/CT scans compared to four out of five 18F-FDG PET/CT scans. Altogether 18F-choline PET/CT detected a total of 134 bone lesions compared to 64 lesions detected by 18F-FDG PET/CT. Interestingly, the vast majority of the missed lesions in 18F-FDG PET/CT were in the axial skeleton including the skull vault [38].

To summarize, choline PET seems to have a better detection rate of focal lesions than 18F-FDG PET. However, no comparison studies between the two PET tracers in previously untreated MM patients have been performed. A limitation of choline PET is its unfavorable physiological distribution involving increased uptake in the bone marrow and the liver parenchyma potentially masking lesions in these organs; although hepatic lesions are rare in MM and can be reliably detected with MRI, the increased activity in the bone marrow compartment may pose significant diagnostic challenges, in particular in patients showing a diffuse bone marrow infiltration pattern. Moreover, the use of 11C-choline is limited in centres with an on-site cyclotron and radiopharmacy facilities, because of the very short half-life of the radioisotope (20 min).
