新型的放射活性的诊断性注射剂Axumin（[F-18] Fluciclovine）用于检测前列腺癌复发，日前获美国FDA批准
FDA的药品评价和研究中心医学影像产品部主任Libero Marzella，M.D.，Ph.D.说：“当PSA处在非常低水平时，影像测试不能确定复发前列腺癌的位置，”。“对这些患者Axumin是提供显示另一个准确影像的方法。”
批准日期：2016年5月27日；公司：Blue Earth Diagnostics，Ltd
AXUMIN(fluciclovine F 18)注射液，为静脉使用
美国初次批准：2016
作用机制
Fluciclovine F 18是一种合成氨基酸通过氨基酸转运蛋白跨越哺乳动物细胞膜转运，例如LAT-1和ASCT2，它们在前列腺癌细胞中被上调。在前列腺癌细胞与周围正常组织比较，Fluciclovine F 18被摄取程度较大。
适应证和用途
Axumin是一种放射性诊断剂适用为在男性根据升高的血前列腺抗原抗原(PSA)水平以前治疗后正电子发射断层扫描(PET)影像有怀疑的前列腺癌复发。
剂量和给药方法
⑴使用适当的辐射安全处置措施。
⑵从其容器无菌地抽吸Axumin和作为静脉推注注射给予370MBq(10mCi).
⑶给药后3-5分钟开始影像。应从大腿-中段和至颅底进行扫描，有一个总扫描时间接近20-30分钟。
⑷在一名成年中伴随Axumin 370MBq(10mCi)被注射的活性有效(辐射吸收)剂量接近8mSv(0.8rem)。
剂型和规格
注射液：
透明，无色溶液一个30mL多-剂量小瓶在校正时间和日期含335-8200MBq/mL(9-221 mCi/mL) fluciclovine F18。
禁忌证
无。
警告和注意事项
用Axumin影像可能发生影像解释错误.
辐射风险：Axumin对患者的长期累计辐射暴露贡献。确保安全处置以保护患者和卫生保健工作者来自无意的辐射暴露。
不良反应
最常见报道不良反应是注射部位疼痛，红斑，和味觉障碍。
如何供应/贮存和处置
如何供应
Axumin是作为一个透明，无色注射液在一个30 mL多-剂量玻璃小瓶含在校正时间和日期时约26 mL溶液的335-8200 MBq/mL(9-221 mCi/mL) fluciclovine F 18供应。
30mL无菌多-剂量小瓶：NDC 69932-001-030
贮存和处置
贮存Axumin在控制室温(USP)20°C至25°C(68°F至77°F)。Axumin不含防腐剂。贮存Axumin在原始容器内在辐射屏蔽中。
这个制备物是被批准由经核管理委员会或有关监管机构的协议状态在许可下人员使用。
Fluciclovine F 18 Injection
1. DESCRIPTION 
1.1 Chemical Characteristics
Fluciclovine F 18 injection contains the fluorine 18 (F 18) labeled synthetic amino acid analog fluciclovine. Fluciclovine F 18 is a radioactive diagnostic agent used with PET imaging. Chemically, fluciclovine F 18 is (1r, 3r)-1-amino- 3[18F]fluorocyclobutane-1-carboxylic acid. The structural formula is:
Molecular weight: 132.1
Fluciclovine F 18 injection is a sterile, non-pyrogenic, clear, colorless, hyperosmolal (approximately 500 - 540 mOsm/kg) injection for intravenous use. Each milliliter contains up to 2 micrograms of fluciclovine, 335 to 8200 MBq (9 to 221 mCi) fluciclovine F 18 at calibration time and date, and 20 mg trisodium citrate in water for injection. The solution also contains hydrochloric acid, sodium hydroxide and has a pH between 4 and 6.
1.2 Physical Characteristics
Fluorine 18 (F 18) is a cyclotron produced radionuclide that decays by positron emission (ß+ decay, 96.7%) and orbital electron capture (3.3%) to stable oxygen 18 with a physical half-life of 109.7 minutes. The positron can undergo annihilation with an electron to produce two gamma rays; the energy of each gamma ray is 511 keV (Table 2).
Table 1: Principal Radiation Produced from Decay of Fluorine 18 Radiation
1.3 External Radiation
The point source air-kerma coefficient for F 18 is 3.75 x 10-17 Gy m2/(Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of 8 cm of Pb will decrease the radiation transmission (i.e., exposure) by a factor of about 10,000.
Table 2: Radiation Attenuation of 511 keV Gamma Rays by Lead Shielding
2. INDICATIONS AND USAGE 
Fluciclovine F 18 injection is indicated for positron emission tomography (PET) in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.
3. DOSAGE AND ADMINISTRATION 
3.1 Radiation Safety - Drug Handling
Fluciclovine F 18 injection is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.3)]. Use waterproof gloves and effective shielding, including syringe shields, when handling and administering fluciclovine F 18 injection.
3.2 Recommended Dose and Administration Instructions
The recommended dose is 370 MBq (10 mCi) administered as an intravenous bolus injection.
• Inspect fluciclovine F 18 injection visually for particulate matter and discoloration before administration. Do not use the drug if the solution contains particulate matter or is discolored.
• Use aseptic technique and radiation shielding when withdrawing and administering fluciclovine F 18 injection.
• Calculate the necessary volume to administer based on calibration time and date, using a suitably calibrated instrument. The recommended maximum volume of injection of undiluted fluciclovine F 18 injection is 5mL.
• Fluciclovine F 18 injection may be diluted with Sodium Chloride Injection, 0.9%.
• After the fluciclovine F 18 injection, administer an intravenous flush of sterile Sodium Chloride Injection, 0.9% to ensure full delivery of the dose.
• Dispose of any unused drug in a safe manner in compliance with applicable regulations.
3.3 Patient Preparation Prior to PET Imaging
• Advise the patient to avoid any significant exercise for at least one day prior to PET imaging.
• Advise patients not to eat or drink for at least 4 hours (other than small amounts of water for taking medications) prior to administration of fluciclovine F 18 injection.
3.4 Image Acquisition Guidelines
Position the patient supine with arms above the head. Begin PET scanning 3 to 5 minutes after completion of the fluciclovine F 18 injection. It is recommended that image acquisition should start from midthigh and proceed to the base of the skull. Typical total scan time is between 20 to 30 minutes.
3.5 Image Display and Interpretation
Localization of prostate cancer recurrence in sites typical for prostate cancer recurrence is based on fluciclovine F 18 uptake in comparison with tissue background. For small lesions (less than 1cm in diameter) focal uptake greater than blood pool should be considered suspicious for prostate cancer recurrence. For larger lesions, uptake equal to or greater than bone marrow is considered suspicious for prostate cancer recurrence.
3.6 Radiation Dosimetry
The radiation absorbed doses estimated for adult patients following intravenous injection of fluciclovine F 18 injection are shown in Table 3. Values were calculated from human biodistribution data using OLINDA/EXM (Organ Level Internal Dose Assessment/Exponential Modeling) software.
The (radiation absorbed) effective dose resulting from the administration of the recommended activity of 370 MBq of fluciclovine F 18 injection is 8 mSv. For an administered activity of 370 MBq (10 mCi), the highest-magnitude radiation doses are delivered to the pancreas, cardiac wall, and uterine wall: 38 mGy, 19 mGy, and 17 mGy, respectively. If a CT scan is simultaneously performed as part of the PET procedure, exposure to ionizing radiation will increase in an amount dependent on the settings used in the CT acquisition.
Table 3: Estimated Radiation Absorbed Doses in Various Organs/Tissues in Adults who Received Fluciclovine F 18 Injection
4. CONTRAINDICATIONS 
None.
5. WARNINGS AND PRECAUTIONS 
5.1 Risk for Image Misinterpretation
Image interpretation errors can occur with fluciclovine F 18 injection PET 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 prostate cancer. The performance of fluciclovine F 18 injection seems to be affected by PSA levels [See Clinical Studies]. Fluciclovine F 18 uptake is not specific for prostate cancer and may occur with other types of cancer and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological eva luation of the suspected recurrence site, is recommended.
5.2 Hypersensitivity Reactions
Hypersensitivity reactions including anaphylaxis may occur in patients who receive fluciclovine F 18 injection. Emergency resuscitation equipment and personnel should be immediately available.
5.3 Radiation Risks
Fluciclovine F 18 injection use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers [see Dosage and Administration (3.1)].
6. ADVERSE REACTIONS 
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trial database for fluciclovine F 18 injection includes data from 877 subjects including 797 males diagnosed with prostate cancer. Most patients received a single administration of fluciclovine F 18 injection, a small number of subjects (n = 50) received up to five administrations of the drug. The mean administered activity was 370 MBq (range, 163 to 485 MBq).
Adverse reactions were reported in ≤1% of subjects during clinical studies with fluciclovine F 18 injection. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
8. USE IN SPECIFIC POPULATIONS 
8.1 Usage in Pregnancy
Risk Summary
Fluciclovine F 18 injection is not indicated for use in females and there is no information on the risk of adverse development outcomes in pregnant women or animals with the use of fluciclovine F 18.
8.2 Lactation
Risk Summary
Fluciclovine F 18 injection is not indicated for use in females and there is no information of the presence of fluciclovine F 18 in human milk.
8.3 Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
8.4 Geriatric Use
Of the total number of patients in clinical studies of fluciclovine F 18 injection, the average age was 66 years with a range of 21 to 90 years. No overall differences in safety or effectiveness were observed between older subjects and younger subjects.
9. OVERDOSAGE 
In case of overdose of fluciclovine F 18 injection, encourage patients to maintain hydration and to void frequently to minimize radiation exposure.
10. MECHANISM OF ACTION 
Fluciclovine F 18 is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters, such as LAT-1 and ASCT2, which are upregulated in prostate cancer cells. Fluciclovine F 18 is taken up to a greater extent in prostate cancer cells compared with surrounding normal tissues.
11. PHARMACODYNAMICS  
Following intravenous administration, the tumor-to-normal tissue contrast is highest between 4 and 10 minutes after injection, with a 61% reduction in mean tumor uptake at 90 minutes after injection.
12. PHARMACOKINETICS  
Distribution
Following intravenous administration, fluciclovine F 18 distributes to the liver (14% of administered activity), pancreas (3%), lung (7%), red bone marrow (12%) and myocardium (4%). With increasing time, fluciclovine F 18 distributes to skeletal muscle.
Excretion
Across the first four hours post-injection, 3% of administered radioactivity was excreted in the urine. Across the first 24 hours post-injection, 5% of administered radioactivity was excreted in the urine.
13. HOW SUPPLIED/STORAGE AND HANDLING 
1) How Available:
a) Brand name: AXUMIN, by Blue Earth Diagnostics.
b) Generic drugs: None.
2) How Supplied:
Axumin is supplied as a clear, colorless injection in a 30 mL multiple-dose glass vial containing approximately 26 mL solution of 335-8200 MBq/mL (9-221 mCi/mL) fluciclovine F 18 at calibration time and date.
30 mL sterile multiple-dose vial: NDC 69932-001-030
3) Storage and Handling:
Store at 20° to 25°C (68° to 77°F). [see USP Controlled Room Temperature].
Axumin does not contain a preservative. Store Axumin within the original container in radiation shielding.
This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State. 
注：以上中文处方资料仅供参考，使用以原处方为准：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=389a502e-a7d5-43dd-b6bf-f022ff23f3b9