Choline C 11

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 Decatur Memorial Hospital at 800-826-2827 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4 CONTRAINDICATIONS None. None ( 4 ).

11 DESCRIPTION 11.1 Chemical Characteristics Choline C11 Injection is a positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with PET imaging. The active ingredient, 11 C-choline, has the molecular formula of C 4 CH 14 NOCl with a molecular weight of 138.63 g and has the following chemical structure: Choline C11 Injection is provided as a ready to use sterile, pyrogen-free, clear and colorless solution. Each milliliter contains 148 MBq to 1225 MBq (4 mCi to 33.1 mCi) of 11 C-choline at EOS calibration time in aqueous 0.9% sodium chloride solution. The pH of the solution is between 4.5 and 7.5. Chemical Structure 11.2 Physical Characteristics Carbon 11 is a cyclotron-produced radionuclide that decays to Boron 11 by positron emission and has a physical half life of 20.4 minutes ( Table 2 ). Table 2: Principal Radiation Emission Data for 11 C * Produced by positron annihilation Radiation / Emission % Per Disintegration Energy Positron (®+) 99.76 960.2 keV (Max.) Gamma (±)* 199.5 511 keV The specific gamma ray constant (point source air kerma coefficient) for 11C-choline is 5.8 R/mCi-hr at 1 cm. Selected coefficients of attenuation are listed in Table 3 as a function of lead shield thickness. For example, the use of 39 mm thickness of lead will attenuate the external radiation by a factor of about 1,000. Table 3: Radiation Attenuation of 511 keV Photons by lead (Pb) shielding Shield Thickness (Pb) mm Coefficient of Attenuation 4 0.5 8 0.25 13 0.1 26 0.01 39 0.001 52 0.0001 Table 4 lists fractions remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide. Table 4: Physical Decay Chart for 11 C * Calibration Time Minutes Fraction Remaining 0* 1.000 5 0.844 10 0.712 15 0.600 20 0.507 25 0.427 30 0.360

2 DOSAGE AND ADMINISTRATION • Aseptically withdraw Choline C 11 Injection from its container and administer 370 to 740 MBq (10 to 20 mCi) as a bolus intravenous injection. The radioactivity dose (370 to 740 MBq, 10 to 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 to 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 to 740 MBq (10 to 20 mCi) administered as a bolus intravenous injection. The radioactivity dose (370 to 740 MBq, 10 to 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 Radiation 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 Per Unit Administered Activity (ìGy/MBq) b a Gastrointestinal b Assumed radiation weighting factor, wr, (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 x 0.0037 = 0.0133 rad/mCi). c Radiation tissue weighting factors, wT, 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 x 0.0037 = 0.0161 rem/mCi). 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 (ìSv/MBq) c 4.35 The effective dose resulting from a 740 MBq (20 mCi) dosage of Choline C 11 Injection is 3.22 mSv in an adult, (740 x 4.35 = 3219 mSv = 3.2 mSv). The use of a CT scan to calculate attenuation correction for reconstruction of 11C-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 11C-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 to 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.

1 INDICATIONS AND USAGE Choline C11 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 Use : 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 Use : 11 C-choline PET imaging is not a replacement for histologic verification of recurrent prostate cancer ( 1 ).

7 DRUG INTERACTIONS 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 ).

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics In a study of men with prostatic hyperplasia or primary prostate cancer, PET imaging showed 11 C-choline radioactivity accumulated rapidly within the prostate; uptake appeared to peak by five minutes following injection of the drug and activity was retained over the subsequent 30 minute scanning period. Little uptake was observed in the bladder and rectum. 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.

12.1 Mechanism of Action 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.

12.2 Pharmacodynamics In a study of men with prostatic hyperplasia or primary prostate cancer, PET imaging showed 11 C-choline radioactivity accumulated rapidly within the prostate; uptake appeared to peak by five minutes following injection of the drug and activity was retained over the subsequent 30 minute scanning period. Little uptake was observed in the bladder and rectum.

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.

20191106

1

3 DOSAGE FORMS AND STRENGTHS Choline C11 Injection contains 148 MBq to 1225 MBq (4 mCi to 33.1 mCi) per milliliter of 11 C-choline at End of Synthesis (EOS) calibration time in aqueous 0.9% sodium chloride solution (approximately 10 mL volume). Choline C11 injection contains 148 MBq to 1225 MBq (4 mCi to 33.1 mCi) per milliliter of 11 C-choline at EOS (End of Synthesis) calibration time in aqueous 0.9% sodium chloride solution (approximately 10 mL volume) ( 3 ).

Choline C 11 Choline C 11 CHOLINE C-11 CHOLINE C-11 SODIUM CHLORIDE

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies have not been performed to evaluate the carcinogenic potential of Choline C 11 Injection. The mutagenic potential of Choline C 11 Injection has not been adequately evaluated; however, any radiopharmaceutical, including Choline C 11 Injection, has the potential to be mutagenic. The effect of Choline C 11 Injection on fertility has not been evaluated.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies have not been performed to evaluate the carcinogenic potential of Choline C 11 Injection. The mutagenic potential of Choline C 11 Injection has not been adequately evaluated; however, any radiopharmaceutical, including Choline C 11 Injection, has the potential to be mutagenic. The effect of Choline C 11 Injection on fertility has not been evaluated.

ANDA206319

Choline C 11

Choline C 11

73410-004

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PRINCIPAL DISPLAY PANEL - Vial Label Vial Label Choline C11 Injection 4 mCi/mL to 33.1 mCi/mL @EOS For Intravenous Use Expires 120 minutes after EOS Lot #: Rx Only NDC# 73410-004-01 Sterile, Non-pyrogenic. Contains 0.14 GBq to 1.22 GBq (4 mCi/mL to 33.1 mCi/mL) @ EOS of no-carrier added Choline C 11 in 0.9% NaCl. Multi-Dose Vial Diagnostic - For Intravenous Use Only. Store @ 25°C (77°F); See Insert. Store upright in shielded container. Aseptically withdraw/handle doses. *EOS - End of Synthesis. Expires 120 minutes after EOS. Calculate correct dosage from date and time of calibration. Do not use if cloudy or contains particulate matter. [11C] Half-life = 20.4 minutes. Manufactured by: Decatur Memorial Hospital Decatur, IL 62526 Caution: Radioactive Material Principal Display Panel - Vial Label

Manufactured by: Decatur Memorial Hospital Center for Advanced Molecular Medicine 2300 North Edward Street, Suite 100 Decatur, IL 62526 Distributed by: Decatur Memorial Hospital Center for Advanced Molecular Medicine 2300 North Edward Street, Suite 100 Decatur, Illinois 62526

17 PATIENT COUNSELING INFORMATION • Instruct patients to drink plenty of water or other fluids (as tolerated) in the four hours before their PET/CT study. • Instruct patients to void after completion of each image acquisition session and as often as possible for one hour after the PET/CT scan ends.

14 CLINICAL STUDIES A systematic review of published reports identified four studies that contained data sufficient to compare 11 C-choline PET imaging to histopathology (truth standard) among patients with suspected prostate cancer recurrence and non-informative conventional imaging (for most patients, CT or MRI). In general, the suspected recurrence criteria consisted of at least two sequential PSA levels of > 0.2 ng/mL for men who had undergone prostatectomy and PSA levels of ≥ 2 ng/mL above the post-therapy nadir for men who had undergone radiotherapy. The studies were predominantly single clinical site experiences and image acquisition generally surveyed radioactivity distribution from the base of the pelvis to the base of the skull. Prospective studies: Two studies examined the ability of 11 C-choline PET/CT to detect prostate cancer in pelvic and/or retroperitoneal lymph nodes among patients who had previously undergone radical prostatectomy. Both studies used a truth standard of lymph node histopathology. 11 C-choline images were interpreted by readers masked to clinical information; surgical resection of lymph nodes was performed by surgeons aware of the 11 C-choline PET/CT results. In Study One 3 , 25 patients who underwent 11 C-choline PET/CT and conventional imaging (CT or MRI) were scheduled to undergo pelvic or pelvic plus retroperitoneal lymphadenectomy following the imaging identification of suspected lymph node metastases. The median PSA was 2.0 ng/mL (range 0.2 to 23.1 ng/mL). The study excluded subjects with metastatic disease detected by bone scintigraphy or isolated prostatic fossa recurrence. Among the 25 patients, 21 had positive 11 C‑choline PET/CT scans; histopathology verified cancer in 19 of these patients. Lymph node histopathology detected no cancer among the four patients who had surgery based only on positive conventional imaging; 11 C-choline PET/CT was negative in all four patients. The study report included information for patients who had non-informative conventional imaging (CT or MRI, bone scintigraphy and transrectal ultrasound), as shown in Table 5 . In Study Two 4 , 15 patients were scheduled to undergo pelvic or pelvis plus retroperitoneal lymphadenectomy solely based upon positive 11 C-choline PET/CT imaging in the setting of negative conventional imaging (ultrasound and/or CT and/or MRI and/or bone scintigraphy). The median PSA was 2.0 ng/mL (range 1.0 to 8.0 ng/mL); all patients had previously undergone radical prostatectomy. Eight of the 15 patients had cancer verified by lymph node histology; histology detected no cancer in seven patients. Retrospective Studies: Two studies were retrospective reviews of patients who underwent 11 C-choline PET/CT and had histopathology obtained from biopsy of the prostatic fossa or other suspected recurrence sites. In Study Three 5 , 11 C-choline PET/CT imaging was performed among 36 patients with suspected prostate cancer recurrence and 13 subjects without suspected recurrence (controls). Prostatic fossa biopsies were performed among the patients with suspected recurrence. All the patients and control subjects had previously undergone radical prostatectomy; patient with suspected recurrence had no evidence of cancer using conventional clinical evaluations, including trans-rectal ultrasound and bone scintigraphy. PET/CT scans were interpreted by readers masked to clinical information. Median PSA was 2.0 ng/mL (range 0.3 - 12.1 ng/mL) for patients with suspected recurrence and 0.1 ng/mL (range 0.0 - 0.2 ng/mL) in control subjects. Prostatic fossa biopsy showed cancer in 33 of the 36 patients with suspected recurrence. PET/CT scans were positive in 25 of the 36 patients; two patients had false positive scans (one scan in a control subject and one scan in a suspected recurrence subject who had no cancer detected on prostatic fossa biopsy). Among the 13 control subjects, 12 had negative PET/CT scans. In Study Four 6,7 , 34 patients with negative conventional imaging underwent 11 C-choline PET/CT and subsequently had biopsies of suspected recurrence sites. The median PSA level of the 34 patients was 3.9 ng/mL (range 0.2 to 65.0 ng/mL); 22 of the patients had previously undergone radical prostatectomy and 12 had received other therapy (radiotherapy, anti-androgen therapy or cryotherapy). 11 C-choline PET/CT images were positive in 30 patients and negative in four patients. Cancer was verified by histopathology in 29 patients; 25 had positive PET/CT images and four had negative PET/CT images. Five patients with positive PET/CT images did not have cancer confirmed with histopathology. As shown in Table 5 , within each study at least half the patients with non-informative conventional imaging had positive 11 C-choline PET/CT images and histologically verified recurrent prostate cancer. Table 5: 11 C-Choline PET/CT Results among Patients with Non-informative Conventional Imaging and a Histopathology Truth Standard * ND = not determined Study Patients, n Total True Positive False Positive True Negative False Negative One 13 11 2 ND* ND* Two 15 8 7 ND* ND* Three 36 23 1 2 10 Four 34 25 5 0 4 In Studies Three and Four, PSA levels were generally lower for patients with negative 11 C-choline PET/CT results than for patients with positive results. In Study Three, the median PSA was 2.6 ng/mL (range 0.6 - 12.1 ng/mL) among the 23 patients with true positive images; nine out of 11 patients with false negative or false positive images had PSA levels < 2 ng/mL. In Study Four, the median PSA was 4.2 ng/mL (range 0.2 - 65.0 ng/mL) among the 25 patients with true positive images; PSA levels < 2 ng/mL were observed in four of the nine patients with false negative or false positive images. These data, combined with other published reports, suggest that 11 C-choline PET imaging performance may be more reliable among patients with blood PSA levels > 2 ng/mL, compared to patients with lower levels.

15 REFERENCES 1. Tolvanen T, Yli-Kerttula T, Ujula T, Autio A, Lehikoinen P, Minn J, Roivinen A; Biodistribution and radiation dosimetry of [ 11 C] choline: a comparison between rat and human data. Eur J Nucl Med Mol Imaging. 2010; 37:874-83. 2. OLINDA/EXM software, Version 1.1. Vanderbilt University, 2007. 3. Scattoni V, Picchio M, Suardi N, Messa C, Freschi M, Roscigno M, Da Pozzo L, Bocciardi A, Rigatti P, Fazio F. Detection of lymph-node metastases with integrated [ 11 C]choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur Urol. 2007; 52:423-9. 4. Rinnab L, Mottaghy FM, Simon J, Volkmer BG, de Petriconi R, Hautmann RE, Wittbrodt M, Egghart G, Moeller P, Blumstein N, Resks S, Kuefer R. [ 11 C]choline PET/CT for targeted salvage lymph node dissection in patients with biochemical recurrence after primary curative therapy for prostate cancer. Urologia Int. 2008; 81:191-7. 5. Reske SN, Blumstein NM, Glatting G. [ 11 C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Med Mol Imaging. 2008; 35:9-17. 6. Mitchell C, Kwon E, Lowe V, Hung J, Rangel L, Karnes RJ. Impact of 11C-choline PET/CT scan on detection of recurrent prostate cancer in men with biochemical recurrence following failed initial treatment; supplemented with subject-level data. J Urol. 2012; 187:e823. 7. Mitchell C, Kwon E, Lowe V, Hung J, Rangel L, Karnes RJ. Detection of consolidated disease recurrences of prostate cancer by 11 C-choline PET/Scan: results confirmed by surgical resection; supplemented with subject-level data. J Urol. 2012; 187:e823.

8.3 Nursing Mothers Choline C11 Injection is not indicated for use in women. It is not known whether Choline C11 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 C11 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 C11 Injection have not been established in pediatric patients.

8.1 Pregnancy There are no adequate and well controlled studies with Choline C11 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 C11 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 C11 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 C11 Injection to a female of child bearing potential. Choline C11 Injection should be given to a pregnant woman only if clearly needed.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy There are no adequate and well controlled studies with Choline C11 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 C11 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 C11 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 C11 Injection to a female of child bearing potential. Choline C11 Injection should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers Choline C11 Injection is not indicated for use in women. It is not known whether Choline C11 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 C11 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 C11 Injection have not been established in pediatric patients.

16 HOW SUPPLIED 16.1 How Supplied Choline C 11 Injection is packaged in a multi-dose glass vial containing between 148 MBq to 1225 MBq (4 mCi to 33.1 mCi) of 11 C- choline at EOS calibration time in aqueous 0.9% sodium chloride solution (approximately 10 mL volume). NDC 73410-004-01 16.2 Storage and Handling Store Choline C 11 Injection at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) (see USP Controlled Room Temperature). Use the solution within 120 minutes of EOS calibration.