Choline C-11

Choline C 11 Injection is indicated for positron emission tomography (PET) imaging of patients with suspected prostate cancer recurrence and non-informative bone scintigraphy, computerized tomography (CT) or magnetic resonance imaging (MRI). In these patients, 11 C-choline PET imaging may help identify potential sites of prostate cancer recurrence for subsequent histologic confirmation. Suspected prostate recurrence is based upon elevated blood prostate specific antigen (PSA) levels following initial therapy. In clinical studies, images were produced with PET/CT coregistration. Limitation of U se: 11 C-choline PET imaging is not a replacement for histologic verification of recurrent prostate cancer. Choline C 11 Injection is a radioactive diagnostic agent for positron emission tomography (PET) imaging of patients with suspected prostate cancer recurrence and non-informative bone scintigraphy, computerized tomography (CT) or magnetic resonance imaging. In these patients, 11 C-choline PET imaging may help identify potential sites of prostate cancer recurrence for subsequent histologic confirmation. Suspected prostate recurrence is based upon elevated blood prostate specific antigen (PSA) levels following initial therapy. In clinical studies, images were produced with PET/CT coregistration. Limitation of U se: 11 C-choline PET imaging is not a replacement for histologic verification of recurrent prostate cancer ( 1 ).

Choline C 11 Injection contains 148 – 1,225 MBq (4 – 33.1 mCi) per milliliter of 11 C-choline at end of synthesis (EOS) calibration time in aqueous 0.9% sodium chloride solution. Choline C 11 Injection contains 148 – 1,225 MBq (4 – 33.1 mCi) per milliliter of 11 C-choline at end of synthesis calibration time in aqueous 0.9% sodium chloride solution ( 3 ).

None. None ( 4 ).

Imaging errors have been reported; blood PSA levels < 2 ng/mL have been associated with poor imaging performance ( 5.1 ). Allergic reactions: have emergency resuscitation equipment and personnel readily available ( 5.2 ). Radiation risk: Choline C 11 Injection contributes to a patient’s long-term cumulative radiation exposure. Ensure safe handling to protect the patient and health care worker ( 5.3 ).

5.1 Imaging Errors Imaging errors have been reported with 11 C-choline PET and PET/CT imaging. A negative image does not rule out the presence of recurrent prostate cancer and a positive image does not confirm the presence of recurrent cancer. 11C-choline uptake is not specific for prostate cancer and may occur with other types of cancer (such as lung carcinoma and brain tumors). Clinical correlation, including histopathological evaluation of the suspected recurrence site, is essential to proper use of the PET imaging information. Blood PSA levels < 2 ng/mL have been associated with poor performance of 11 C-choline PET imaging (higher numbers of false positive and false negative results) [see Clinical Studies (14) ] . Tissue inflammation as well as prostatic hyperplasia have been associated with false positive 11 C-choline PET images. Concomitant colchicine or androgen-deprivation therapeutic drugs (such as luteinizing hormone-releasing analogs and anti-androgen drugs) may interfere with 11 C-choline PET imaging. One published report of 18 F-methylcholine PET imaging indicated that discontinuation of colchicine for two weeks resolved the colchicine effect. The impact of discontinuation of androgen-deprivation therapy upon 11 C-choline PET imaging has not been established [see Drug Interactions (7) ] .

5.2 Allergic Reactions As with any injectable drug product, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available.

5.3 Radiation Risks Choline C 11 Injection contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Safe handling should be ensured to minimize radiation exposure to the patient and health care workers [ see Dosage and Administration (2.1) ].

Exclusive of an uncommon, mild injection site reaction, no adverse reactions to 11 C-choline have been reported. Exclusive of an uncommon, mild injection site reaction, no other adverse reactions have been reported ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Division of Nuclear Medicine, Department of Radiology, Mayo Clinic at 507-284-2511 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Colchicine and androgen-deprivation therapeutic drugs have been reported to interfere with choline-based PET imaging [ see Warnings and Precautions (5.1) ]. The impact of androgen-deprivation therapeutic drugs upon 11 C-choline PET imaging may depend upon the hormonal responsiveness of a patient’s recurrent prostate cancer. Clinical studies have not established this relationship but published reports suggest 11 C-choline PET imaging may be productive in patients with “hormone resistant” recurrent prostate cancer even if the patients are receiving anti-androgen therapy. Imaging may prove unproductive or misleading due to failed or insufficient 11 C-choline uptake in patients with hormone-responsive cancer if the patients are receiving androgen-deprivation therapy. Colchicine and androgen-deprivation therapeutic drugs may interfere with 11 C-choline PET/CT imaging performance ( 5.1 ).

8.1 Pregnancy Pregnancy Category C. There are no adequate and well controlled studies with Choline C 11 Injection in pregnant women and the fetal radiation dose from a 11 C-choline PET imaging study is unknown. It is not known whether Choline C 11 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with 11 C-choline. All radiopharmaceuticals, including Choline C 11 Injection, have a potential to cause fetal harm. The likelihood of fetal harm depends on the stage of fetal development and the magnitude of the radiopharmaceutical dose. Assess pregnancy status before administering Choline C 11 Injection to a female of child bearing potential. Choline C 11 Injection should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers Choline C 11 Injection is not indicated for use in women. It is not known whether Choline C 11 Injection is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Choline C 11 Injection, nursing mothers should use alternative infant nutrition sources (e.g., stored breast milk or infant formula) and pump and discard breast milk for 8 hours (>10 half lives of radioactive decay for 11 C isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use The safety and effectiveness of Choline C 11 Injection have not been established in pediatric patients.

Choline C 11 Injection is a radiolabeled analog of choline, a precursor molecule essential for the biosynthesis of cell membrane phospholipids. Choline is involved in synthesis of the structural components of cell membranes, as well as modulation of trans-membrane signaling. Increased phospholipid synthesis (i.e., increased uptake of choline) has been associated with cell proliferation and the transformation process that occurs in tumor cells.