Choline C-11

1 INDICATIONS AND USAGE 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 ).

2 DOSAGE AND ADMINISTRATION Aseptically withdraw Choline C 11 Injection from its container and administer 370 – 740 MBq (10 – 20 mCi) as a bolus intravenous injection. The radioactivity dose (370 – 740 MBq, 10 – 20 mCi) is chosen based on patient body dimensions and the characteristics of the image acquisition system ( 2.1 ). Initiate imaging immediately after administration of Choline C 11 Injection and acquire static emission images 0 – 15 minutes from the time of injection ( 2.5 ). The effective radiation absorbed dose from 740 MBq (20 mCi) dose of Choline C 11 Injection is approximately 3.22 mSv (0.32 rem) in an adult ( 2.4 ). Image interpretation: Refer to full prescribing information ( 2.5 ). 2.1 Radiation Safety – Drug Handling Choline C 11 Injection is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure during administration. Use waterproof gloves and effective shielding when handling Choline C 11 Injection. Radiopharmaceuticals, including Choline C 11 Injection, should only be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. 2.2 Recommended Dose and Administration Instructions The recommended dose is 370 – 740 MBq (10 – 20 mCi) administered as a bolus intravenous injection. The radioactivity dose (370 – 740 MBq, 10 – 20 mCi) is chosen based on patient body dimensions and the characteristics of the image acquisition system Inspect Choline C 11 Injection visually for particulate matter and discoloration before administration. Do not use the drug if the solution contains particulate matter or is discolored. Aseptically withdraw Choline C 11 Injection from its container and administer the drug as a bolus through a peripheral venous catheter. Dispose of any unused drug in a safe manner, in compliance with applicable regulations. 2.3 Patient Preparation Prior to administration of Choline C 11 Injection: Fasting for at least six hours is recommended to minimize the potential for dietary choline interference with radioactivity uptake in tissue. Ensure that the patient is well hydrated and encourage voiding when imaging is completed. 2.4 R adiation Dosimetry The estimated radiation absorbed doses for adults from intravenous injection of Choline C 11 Injection are shown in Table 1. These estimates are calculated from data in Tolvanen 1 and using OLINDA/EXM (Organ Level Internal Dose Assessment/Exponential Modeling) software from Vanderbilt University. 2 Table 1: Estimated Radiation Absorbed Dose Per Unit Activity for Adults, Choline C 11 Injection Organ/Tissue Mean Absorbed Dose P er Unit Administered Activity ( μ Gy/MBq) b Adrenals 3.59 Bone - Osteogenic Cells 4.81 Bone - Red Marrow 1.90 Brain 1.16 Breast 1.39 Gallbladder Wall 4.54 GI a – Lower Large Intestine Wall 1.81 GI a - Small Intestine 2.35 GI a - Stomach Wall 6.00 GI a – Upper Large Intestine Wall 6.41 Heart wall 3.43 Kidneys 20.62 Liver 20.11 Lungs 4.59 Muscle 2.54 Ovaries 2.02 Pancreas 29.19 Skin 1.22 Spleen 9.16 Testes 1.36 Thymus 1.69 Thyroid 1.49 Urinary Bladder Wall 3.41 Uterus 1.96 Total body 2.97 Effective Dose (μSv/MBq) c 4.35 a Gastrointestinal b Assumed radiation weighting factor, w r , (formerly defined as quality factor, Q) of 1 for conversion of absorbed dose (Gray or rad) to dose equivalent (Sieverts or rem) for C 11. To obtain radiation absorbed dose in rad/mCi from the above table, multiply the dose in μGy/MBq by 0.0037, (e.g., 3.59 μGy/MBq × 0.0037 = 0.0133 rad/mCi). c Radiation tissue weighting factors, w T , used in the calculation of effective dose are from 1990 Recommendations of the International Commission on Radiological Protection, ICRP Publication 60 (1991). To obtain radiation absorbed dose in rem/mCi from above table, multiply the dose in μGy/MBq by 0.0037, (e.g., 4.35 μGy/MBq × 0.0037 = 0.0161 rem/mCi). The effective dose resulting from a 740 MBq (20 mCi) dosage of Choline C 11 Injection is 3.22 mSv in an adult, (740 × 4.35 = 3219 μSv = 3.2 mSv). The use of a CT scan to calculate attenuation correction for reconstruction of 11 C-choline images (as done in PET/CT imaging) will add radiation exposure. Based upon current scanning techniques, an effective dose of 5.8 mSv would be added from CT scanning. The actual radiation dose is operator, scanner, and patient dependent. The total radiation exposure from 11 C-choline administration and subsequent scan on a PET/CT scanner is estimated to be 9.0 mSv (3.2 mSv + 5.8 mSv). 2.5 Imaging Guidelines Initiate image acquisition immediately after administration of Choline C 11 Injection. Imaging is typically performed from the base of the pelvis to the base of the skull. Acquire static emission images 0 – 15 minutes from the time of injection. Localized uptake of 11 C-choline in a site suspicious for prostate cancer recurrence (a positive image) is determined by comparison of the anatomical relationship of concentrated radioactivity to the neighboring tissue background, exclusive of the radioactivity physiologically accumulated within the pancreas, liver, spleen, kidney and colon.

6 ADVERSE REACTIONS 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

12.3 Pharmacokinetics Distribution: 11 C-choline distributes mainly to the pancreas, kidneys, liver, spleen and colon [ see Dosage and Administration (2.4) ]. Based upon the relatively low urinary excretion of radioactivity, renal distribution is predominantly to the organ itself, rather than via formation of urine. Metabolism: Following intravenous administration, 11 C-choline undergoes metabolism resulting in the detection of 11 C-betaine as the major metabolite in blood. In a study of patients with prostate cancer or brain disorders, the fractional activities of 11 C-choline and 11 C-betaine in human arterial plasma appeared to reach a plateau within 25 minutes, with 11 C-betaine representing 82± 9% of the total 11 C detected at that time point. A small amount of unmetabolized 11 C-choline was detected within the blood at the final sampling time point (40 minutes). Elimination: Urinary excretion of 11 C-choline was < 2% of the injected radioactivity at 1.5 hours after injection of the drug. The rate of 11 C-choline excretion in urine was 0.014 mL/min.