Professional Drug Information > Water O 15

Water O 15 (Systemic)

VA CLASSIFICATION
Primary: DX201

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

^†Not commercially available in Canada.

Category:


Diagnostic aid, radioactive (brain disorders; cardiac disorders)—

Indications

Note: Because water O 15 is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product.


Accepted

—[Brain imaging, positron emission tomographic]¹—Water O 15 is used with positron emission tomography (PET) to quantify regional cerebral blood flow (rCBF), which may be useful to characterize the altered brain perfusion in patients with cerebrovascular disease ^{{01} {05} {06} {07} {12} {13} {16} {23} {26}}.

—[Cardiac imaging, positron emission tomographic]¹—Water O 15 may be used with PET in studies of myocardial perfusion in various physiological and pathological states ^{{10} {11} {23} {26}} to quantify regional myocardial blood flow (rMBF) ^{{08} {10} {11} {14} {17}}. Also, water O 15 may be used rarely with PET to measure perfusable tissue fraction and arterial blood volume ^{{22} {23}}.

¹ Not included in Canadian product labeling.

Physical Properties

Nuclear Data ^{{01} {18} {26}}

Radionuclide (half-life)	Mode of decay	Principal photon emissions (keV)	Mean number of photons/ disintegration
O 15 (2.05 min)	Positron decay	Annihilation* (511)	2

^* The annihilation photons emitted in opposite directions at the moment of positron annihilation are used for imaging purposes. Detection devices usually used are positron emission tomography (PET) units; however, conventional planar scintillation cameras equipped with coincidence circuitry or high-energy collimators have been used for some studies ^{26}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Source—Oxygen-15 is most often generated through the ¹⁴N(d,n) ¹⁵O reaction by means of deuterons accelerated to an energy of 7 to 8 MeV using a cyclotron ^{{01} {05} {07}}. Water O 15 is most commonly prepared from [ ¹⁵O]oxygen by reaction with hydrogen using a palladium catalyst ^{{01} {05}}. Other methods for the production of oxygen-15 and for the preparation of water O 15 also have been developed ^{{07} {10} {19} {23}}.

Mechanism of action/Effect:

The mechanism of action of water O 15 is based on the distribution and clearance of water from the tissues ^{05}.

Brain imaging—Water O 15 is an inert tracer ^{{01} {05}}. It is freely diffusible (approximately 95% extraction fraction in primates under normal blood flow conditions) across the blood-brain barrier; thus, the delivered tracer can diffuse quickly into the extravascular space ^{{05} {23}}. Due to the small size of the water molecule, the distribution of water O 15 in the brain reflects the tissue perfusion at the capillary level. Since water O 15 is not chemically trapped in tissue, it will be cleared gradually from the tissue by blood flow; the larger the blood flow, the faster the clearance occurs ^{05}. In order for the initial images to better reflect the local cerebral blood flow distribution, a shorter imaging time may be used to help lessen the amount of clearance of the tracer; thus, in some studies a sequence of 2-minute PET images for up to 10 minutes has been used to get more photon counts (less random noise) ^{{05} {23}}. When multiple short-time images are used, the radioactivity distribution does not change much and can be considered stationary ^{05}.

Cardiac imaging—Water O 15 is essentially a freely diffusible tracer in the heart (nearly 100% extraction fraction) ^{{10} {24} {25}}. It is promptly washed out as it enters the heart muscle in proportion to the regional blood flow ^{10}. Its uptake does not vary despite changes in myocardial metabolic state ^{{10} {11}}.

Distribution:

Water O 15 approaches a distribution similar to the distribution volume of water in tissue ^{05}.

Brain imaging—Initially, water O 15 is transported to brain tissue in proportion to blood flow ^{{05} {17}}. Subsequently, the larger amounts of tracer transported to the higher flow tissues are cleared faster by the high blood flows, thereby resulting in a quick loss of contrast between brain gray and white matter in the later images ^{05}. After the first minute, the clearance of water O 15 from tissue is expected to be more than the delivery ^{05}. In one study, the radioactivity in tissue decreased at a rate of about 52% and 39% per minute (not decay-corrected), respectively, at 2 and 5 minutes after water O 15 administration ^{05}. After about 10 minutes of a constant infusion of water O 15, the net delivery of tracer by blood flow to brain tissue and the physical decay of the short-lived ¹⁵O in tissue reach an equilibrium ^{05}.

Cardiac imaging—Water O 15 is freely diffusible and it is promptly washed out as it enters the heart muscle ^{{10} {23}}.

Time to peak concentration:

Brain imaging—Approximately 20 to 30 seconds after intravenous bolus administration of water O 15 ^{{05} {23}}. The concentration drops quickly during the first minute ^{05}. After the first minute, the clearance of water O 15 from tissue is more than the delivery ^{05}.

Time to peak diagnostic effect

Time to radioactivity visualization—Immediately at the onset of water O 15 administration ^{{05} {07} {11} {12}}.

Brain imaging—The turnover time of water O 15 in brain tissue is approximately 1 to 2 minutes ^{05}. The optimal imaging time for obtaining the maximal signal-to-noise ratio in cerebral blood flow has been found to be the interval from 90 to 120 seconds ^{15}. For quantitative regional cerebral blood flow (rCBF) imaging procedures involving arterial blood sampling, data acquisition usually is initiated immediately after injection of water O 15 as a continuous series of multi-second frames ^{23}.

Note: Because of the fast physical decay of O 15, the later images have a higher noise level than earlier ones, and thus have limited value for showing the relative distribution volume of water in brain tissues ^{05}. After 10 minutes, the photon counting noise is too large to give any useful information ^{05}.


Radiation dosimetry:
^{21}

Estimated absorbed radiation dose*
Organ	mGy/MBq (mean)	rad/mCi
Heart wall	0.002	0.008
Kidneys	0.002	0.007
Lungs	0.002	0.007
Thyroid	0.002	0.006
Pancreas	0.002	0.006
Spleen	0.002	0.006
Liver	0.002	0.006
Brain	0.001	0.005
Adrenals	0.001	0.005
Small intestine	0.001	0.005
Red marrow	0.0009	0.003
Large intestine wall, lower	0.0007	0.003
Large intestine wall, upper	0.0007	0.003
Testes	0.0007	0.003
Stomach	0.0005	0.002
Bone surfaces	0.0005	0.002
Gallbladder wall	0.0005	0.002
Ovaries	0.0004	0.001
Thymus	0.0004	0.001
Uterus	0.0003	0.001
Breasts	0.0003	0.001
Muscle	0.0003	0.001
Skin	0.0003	0.001
Urinary bladder wall	0.0002	0.0008
Effective dose: 0.001 mSv/MBq (0.004 rem/mCi)

^* For adults; intravenous injection ^{21}. Data based on the Radiopharmaceutical Internal Dose Information Center, February 1993. Oak Ridge Institute for Science and Education.

Elimination:
    Water—Various routes, including renal, fecal, respiratory, and epidermal ^{23}.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Studies to assess transplacental transfer of water O 15 have not been done in humans; however, such transfer almost certainly occurs, given the free diffusibility of water O 15 ^{23}. The possibility of pregnancy should be assessed in women of childbearing potential. Clinical situations exist where the benefit to the patient and fetus, based on information derived from radiopharmaceutical use, outweighs the risks from fetal exposure to radiation. In this situation, the physician should use discretion and reduce the administered activity to the lowest practical amount. ^{03}

Breast-feeding

Water O 15 is expected to be distributed into breast milk ^{{23} {26}}. Due to the short physical half-life of water O 15, excretion of this agent during lactation is unlikely to result in significant radiation exposure to the breast-feeding infant ^{{23} {26}}.

Pediatrics

Appropriate studies on the relationship of age to the effects of water O 15 have not been performed in the pediatric population.


Geriatrics


Appropriate studies on the relationship of age to the effects of water O 15 have not been performed in the geriatric population. However, studies that included older patients were conducted, and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected ^{{11} {13} {15}}.

Drug interactions and/or related problems
There are no known drug interactions and/or related problems associated with the use of water O 15.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

There is no information regarding medical problems that would present an increased risk or interfere with the use of water O 15.


Side/Adverse Effects
There are no known side/adverse effects associated with the use of water O 15 ^{05}.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic) .
In providing consultation, consider emphasizing the following selected information (>> = major clinical significance):

Description of use
Action in the body: Concentration of radioactivity in tissues, according to blood flow, may be visualized by external imaging

Small amounts of radioactivity used in diagnosis; radiation received is low and considered safe

Before having this test
»   Conditions affecting use, especially:

Pregnancy—Risk to fetus from radiation exposure as opposed to benefit derived from use should be considered

Preparation for this test
Nuclear medicine department should advise patient on any preparatory instructions

Precautions after having this test
No special precautions needed


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the appropriate federal or state regulatory agency, if required, or, outside the U.S., the appropriate authority ^{04}.

For brain imaging
Depending on the technique used, a series of blood samples may be withdrawn from the radial artery over a period of about 10 minutes after water O 15 administration ^{05}. These samples are then counted in a well counter to give an input function, which, together with the projection data collected from positron emission tomography (PET), is processed to provide quantitative information about local cerebral blood flow and local water distribution volumes ^{{05} {06} {12} {23}}.

For cardiac imaging
Blood pool subtraction is required for myocardial perfusion imaging with water O 15 since water O 15 promptly begins to be washed out as it enters the heart muscle; therefore, a large amount of activity from the blood pool contaminates the myocardial perfusion phase images ^{{10} {11}}. After the water O 15 study blood pool images may be obtained by the inhalation of labeled carbon monoxide gas, which labels the hemoglobin in the red blood cells ^{{10} {11} {23}}.

Safety considerations for handling this radiopharmaceutical
Guidelines for the receipt, storage, handling, dispensing, and disposal of radioactive materials are available from scientific, professional, state, federal, and international bodies. Handling of this radiopharmaceutical should be limited to those individuals who are appropriately qualified and authorized ^{02}.


Parenteral Dosage Forms

WATER O 15 INJECTION USP

Note: Because water O 15 is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product.


Usual adult and adolescent administered activity
[Brain imaging]¹
Intravenous, 1110 to 1850 megabecquerels (30 to 50 millicuries) via the antecubital vein as a bolus injection ^{{05} {12}}.

Note: Depending on the technique used, arterial blood samples may be required to determine regional cerebral blood flow from the regional tissue radiotracer concentration recorded by PET ^{{05} {12}}.


[Cardiac imaging]¹
Intravenous, 18.5 megabecquerels (0.5 millicurie) per kg of body weight, or 555 to 1110 megabecquerels (15 to 30 millicuries), administered via the cubital vein as a bolus injection ^{{08} {10} {11}}.

Note: In studies of regional myocardial perfusion, there is a need to label the blood pool with C ¹⁵O after the water O 15 study to minimize inaccuracies in subtraction that may result from a change in cardiac dimensions ^{11}.
The administration of water O 15 by slow (2 minutes) infusion provides another alternative to the bolus injection protocol by which to obtain regional myocardial blood flow and perfusable tissue fraction values with an acceptable degree of accuracy ^{22}.



Usual pediatric administered activity
[Brain imaging]¹ —
Intravenous, 25.9 megabecquerels (0.7 millicurie) per kg of body weight as a bolus injection ^{09}.


Usual geriatric administered activity
See Usual adult and adolescent administered activity .

Strength(s) usually available
U.S.—
Prepared on-site at various clinical facilities.

Canada—
Prepared on-site at various clinical facilities.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Unless otherwise specified by the supplier, it is prudent to avoid extreme temperatures ^{26}.


Caution:
Radioactive material.

Developed: 04/19/1999

References

1. Stöcklin G, Pike VW, editors. Radiopharmaceuticals for positron emission tomography: methodological aspects. Boston: Kluwer Academic Publishers; 1993. p. 2, 12-3, 121, 127-8.
   

2. Radiopharmaceuticals Advisory Panel Meeting, 4/96.
   

3. Radiopharmaceuticals Advisory Panel Meeting, 5/8/91.
   

4. Radiopharmaceuticals Advisory Panel Meeting, 8/4/92.
   

5. Huang SC, Carson RE, Hoffman EJ, et al. Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and ¹⁵O-water. J Cereb Blood Flow Metab 1983 Jun; 3(2): 141-53.
   

6. Fox PT, Mintun MA, Raichle ME, et al. A noninvasive approach to quantitative functional brain mapping with H ₂ ¹⁵O and positron emission tomography. J Cereb Blood Flow Metab 1984 Sep; 4(3): 329-33.
   

7. Ter-Pogossian MM, Herscovitch P. Radioactive oxygen-15 in the study of cerebral blood flow, blood volume, and oxygen metabolism. Semin Nucl Med 1985 Oct; 15(4): 377-94.
   

8. Takahashi A, Iida H, Ono Y, et al. Regional myocardial blood flow quantitatively measured using O-15 water and dynamic positron emission tomography. J Cardiol 1987 Dec; 17(4): 741-8.
   

9. Powers WJ, Stabin M, Howse D, et al. Radiation absorbed dose estimates for oxygen-15 radiopharmaceuticals (H ₂ ¹⁵O, C ¹⁵O, O ¹⁵O) in newborn infants. J Nucl Med 1988 Dec; 29(12): 1961-70.
   

10. Senda M, Nishizawa S, Yonekura Y, et al. A new subtraction method for obtaining myocardial perfusion images with oxygen-15 water and positron emission tomography. Ann Nucl Med 1988 Nov; 2(2): 101-6.
    

11. Walsh MN, Bergmann SR, Steele RL, et al. Delineation of impaired regional myocardial perfusion by positron emission tomography with H ₂ ¹⁵O. Circulation 1988 Sep; 78(3): 612-20.
    

12. Herholz K, Pietrzyk U, Wienhard K, et al. Regional cerebral blood flow measurement with intravenous [ ¹⁵O]water bolus and [ ¹⁸F]fluoromethane inhalation. Stroke 1989 Sep; 20(9): 1174-81.
    

13. Frackowiak RS, Friston KJ. Functional neuroanatomy of the human brain: positron emission tomography—a new neuroanatomical technique. J Anat 1994 Apr; 184(Pt 2): 211-25.
    

14. Bergmann SR, Herrero P, Markham J, et al. Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol 1989 Sep; 14(3): 639-52.
    

15. Kanno I, Iida H, Miura S, et al. Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow. J Nucl Med 1991 Oct; 32(10): 1931-4.
    

16. Duncan DB, Herholz K, Pietrzyk U, et al. Regional cerebral blood flow and metabolism in Sturge-Weber disease. Clin Nucl Med 1995 Jun; 20(6): 522-3.
    

17. Beanlands R. Positron emission tomography in cardiovascular disease. Can J Cardiol 1996 Oct; 12(10): 875-83.
    

18. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed. (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention Inc; 1994. p. 1135.
    

19. Van Naemen J, Monclus M, Damhaut P, et al. Production, automatic delivery and bolus injection of [ ¹⁵O]water for positron emission tomography studies. Nucl Med Biol 1996 May; 23(4): 413-6.
    

20. vom Dahl J. Examination of myocardial perfusion with positron emission tomography: a clinically useful and valid method? Herz 1997 Feb; 22(1): 1-15.
    

21. Radiation Internal Dose Information Center. Oak Ridge Institute for Science and Education. Oak Ridge, TN.
    

22. Iida H, Takahashi A, Tamura Y, et al. Myocardial blood flow: comparison of oxygen-15-water bolus injection, slow infusion and oxygen-15-carbon dioxide slow inhalation. J Nucl Med 1995 Jan; 36(1): 78-85.
    

23. Reviewers' comments per monograph revision of 6/8/98.
    

24. Bergmann SR, Fox KA, Rand AL, et al. Quantification of regional myocardial blood flow in vivo with H ₂ ¹⁵O. Circulation 1984 Oct; 70(4): 724-33.
    

25. Bergmann SR. Clinical applications of myocardial perfusion assessments made with oxygen-15 water and positron emission tomography. Cardiology 1997 Jan-Feb; 88(1): 71-9.
    

26. Advisory Panel consensus per 10/28/98 meeting.
    

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