<s>
Oxygen-15	B-Algorithm
labelled	I-Algorithm
water	I-Algorithm
(	O
also	O
known	O
as	O
15O-water	B-Algorithm
,	O
[O-15]-H2O,	O
or	O
H215O	O
)	O
is	O
a	O
radioactive	O
variation	O
of	O
regular	O
water	O
,	O
in	O
which	O
the	O
oxygen	O
atom	O
has	O
been	O
replaced	O
by	O
oxygen-15	O
(	O
15O	O
)	O
,	O
a	O
positron-emitting	O
isotope	O
.	O
</s>
<s>
15O-water	B-Algorithm
is	O
used	O
as	O
a	O
radioactive	O
tracer	O
for	O
measuring	O
and	O
quantifying	O
blood	O
flow	O
using	O
positron	B-Application
emission	I-Application
tomography	I-Application
(	O
PET	O
)	O
in	O
the	O
heart	O
,	O
brain	O
and	O
tumors	O
.	O
</s>
<s>
Due	O
to	O
its	O
free	O
diffusibility	O
,	O
15O-water	B-Algorithm
is	O
considered	O
the	O
non-invasive	O
gold	O
standard	O
for	O
quantitative	O
myocardial	O
blood	O
flow	O
(	O
MBF	O
)	O
studies	O
and	O
has	O
been	O
used	O
as	O
reference	O
standard	O
for	O
validations	O
of	O
other	O
MBF	O
quantification	O
techniques	O
,	O
such	O
as	O
single-photon	O
emission	O
computed	O
tomography	O
(	O
SPECT	O
)	O
,	O
cardiac	B-Algorithm
magnetic	I-Algorithm
resonance	I-Algorithm
imaging	I-Algorithm
(	O
CMR	O
)	O
and	O
dynamic	O
computed	O
tomography	O
(	O
CT	O
)	O
.	O
</s>
<s>
15N(p,n )	O
15O	O
,	O
in	O
which	O
low-energy	O
protons	B-Application
( ≈5MeV	O
)	O
are	O
used	O
to	O
transmute	O
nitrogen	O
into	O
oxygen-15	O
,	O
or	O
16O(p,pn )	O
15O	O
in	O
which	O
high-energy	O
protons	B-Application
(	O
>16.6MeV	O
)	O
are	O
used	O
.	O
</s>
<s>
The	O
conversion	O
of	O
the	O
oxygen	O
gas	O
[15O]O2	O
to	O
15O-water	B-Algorithm
can	O
happen	O
in	O
two	O
ways	O
:	O
the	O
in-target	O
production	O
and	O
the	O
out-of-target	O
external	O
conversion	O
.	O
</s>
<s>
The	O
in-target	O
production	O
method	O
uses	O
a	O
small	O
amount	O
of	O
hydrogen	O
(	O
about	O
5%	O
)	O
that	O
is	O
added	O
to	O
the	O
gas	O
,	O
whereby	O
15O-water	B-Algorithm
is	O
formed	O
and	O
trapped	O
in	O
a	O
cooled	O
stainless	O
steel	O
loop	O
.	O
</s>
<s>
By	O
heating	O
the	O
loop	O
the	O
15O-water	B-Algorithm
will	O
get	O
released	O
and	O
will	O
be	O
trapped	O
again	O
in	O
a	O
saline	O
solution	O
.	O
</s>
<s>
However	O
,	O
this	O
method	O
requires	O
high-energy	O
protons	B-Application
and	O
is	O
therefore	O
used	O
less	O
.	O
</s>
<s>
Palladium	O
is	O
typically	O
used	O
as	O
a	O
catalyst	B-Device
to	O
lower	O
the	O
activation	O
energy	O
.	O
</s>
<s>
The	O
mixture	O
of	O
the	O
target	O
gas	O
,	O
the	O
catalyst	B-Device
and	O
H2	O
is	O
then	O
heated	O
up	O
,	O
which	O
results	O
in	O
a	O
release	O
of	O
15O-water	B-Algorithm
vapor	O
,	O
which	O
then	O
bubbles	O
into	O
a	O
saline	O
solution	O
and	O
is	O
drawn	O
into	O
a	O
syringe	O
where	O
it	O
can	O
be	O
applied	O
to	O
the	O
subject	O
.	O
</s>
<s>
Oxygen-15	O
decays	O
with	O
a	O
half-life	B-Application
of	O
about	O
2.04minutes	O
to	O
nitrogen-15	O
,	O
emitting	O
a	O
positron	O
.	O
</s>
<s>
The	O
positron	O
quickly	O
annihilates	O
with	O
an	O
electron	O
,	O
producing	O
two	O
gamma	O
rays	O
of	O
about	O
511keV	O
which	O
are	O
detectable	O
using	O
a	O
PET	B-Application
scanner	I-Application
.	O
</s>
<s>
Of	O
several	O
available	O
PET	O
tracers	O
for	O
quantification	O
of	O
myocardial	O
blood	O
flow	O
(	O
MBF	O
)	O
,	O
82Rb	B-Algorithm
,	O
13NH3	O
,	O
and	O
H215O	O
are	O
most	O
commonly	O
used	O
.	O
</s>
<s>
15O-water	B-Algorithm
features	O
different	O
properties	O
compared	O
to	O
82Rb	B-Algorithm
and	O
13NH3	O
.	O
</s>
<s>
15O-water	B-Algorithm
is	O
metabolically	O
inert	O
and	O
diffuses	O
freely	O
across	O
the	O
myocyte	O
membrane	O
in	O
contrast	O
to	O
82Rb	B-Algorithm
and	O
13NH3	O
,	O
which	O
enter	O
the	O
cell	O
via	O
active	O
diffusion	O
(	O
13NH3	O
diffuses	O
both	O
actively	O
and	O
passively	O
)	O
.	O
</s>
<s>
15O-water	B-Algorithm
has	O
a	O
100%	O
extraction	O
rate	O
,	O
which	O
makes	O
15O-water	B-Algorithm
superior	O
to	O
82Rb	B-Algorithm
and	O
13NH3	O
as	O
no	O
flow-dependent	O
extraction	O
corrections	O
are	O
required	O
.	O
</s>
<s>
Its	O
2-minute	O
half-life	B-Application
makes	O
it	O
possible	O
to	O
acquire	O
multiple	O
image	O
scans	O
in	O
rapid	O
sequence	O
.	O
</s>
<s>
However	O
,	O
due	O
to	O
the	O
complete	O
extraction	O
and	O
free	O
diffusibility	O
,	O
15O-water	B-Algorithm
is	O
not	O
retained	O
in	O
the	O
tissue	O
of	O
interest	O
and	O
post-processing	O
is	O
required	O
to	O
convert	O
15O-water	B-Algorithm
images	O
to	O
quantitative	O
blood	O
flow	O
images	O
.	O
</s>
<s>
A	O
technical	O
limitation	O
of	O
15O-water	B-Algorithm
is	O
the	O
challenge	O
in	O
separating	O
the	O
blood	O
activity	O
from	O
the	O
myocardial	O
tissue	O
activity	O
.	O
</s>
<s>
15O-water	B-Algorithm
has	O
now	O
been	O
used	O
in	O
several	O
clinical	O
trials	O
(	O
pivotal	O
studies	O
)	O
.	O
</s>
<s>
A	O
cyclotron	O
is	O
necessary	O
for	O
the	O
production	O
of	O
15O-water	B-Algorithm
,	O
requiring	O
large	O
capital	O
investment	O
in	O
hardware	O
and	O
skilled	O
staff	O
to	O
operate	O
the	O
production	O
.	O
</s>
<s>
However	O
,	O
ongoing	O
development	O
aims	O
to	O
reduce	O
the	O
capital	O
expenditure	O
and	O
limit	O
the	O
amount	O
of	O
skilled	O
personnel	O
involved	O
in	O
the	O
production	O
,	O
making	O
15O-water	B-Algorithm
available	O
for	O
clinical	O
practice	O
.	O
</s>
<s>
The	O
clinical	O
use	O
of	O
15O-water	B-Algorithm
in	O
routine	O
is	O
not	O
widespread	O
.	O
</s>
<s>
Within	O
the	O
European	O
Union	O
,	O
15O-water	B-Algorithm
is	O
recognized	O
as	O
a	O
radiopharmaceutical	B-Algorithm
and	O
regulated	O
as	O
a	O
drug	O
.	O
</s>
<s>
A	O
pharmacopeia	O
monograph	O
exists	O
,	O
allowing	O
hospital	O
facilities	O
to	O
produce	O
and	O
use	O
15O-water	B-Algorithm
within	O
the	O
confines	O
of	O
their	O
national	O
legislation	O
.	O
</s>
<s>
In	O
the	O
US	O
,	O
15O-water	B-Algorithm
is	O
recognized	O
as	O
a	O
radiopharmaceutical	B-Algorithm
and	O
regulated	O
as	O
a	O
drug	O
,	O
but	O
no	O
pharmacopeia	O
monograph	O
exists	O
currently	O
.	O
</s>
