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Titlecyclotron produced short-lived isotopes in nuclear medicine carbon-i1 amino acids
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RIJKSUNIVERSITEIT TE GRONINGEN

CYCLOTRON PRODUCED SHORT-LIVED ISOTOPES
IN NUCLEAR MEDICINE

CARBON-I1 AMINO ACIDS

PROEFSCHRIFT

TIR Vl.RKRIJGING VAN UIT DOCTORAAT IN DK
W1SKUNDL- UN N A T U U R W I T Ü N S C H A P P I N

AAN Di: RIJKSUNIVERSITEIT TKGRONING IN
OP GEZAG VAN DK RECTOR MAGNIIICUS

DR. A. WATTIiL IN HETOPI-NBAAR TE VI-RDI-IDIGKN OP
MAANDAG 8 JULI 1974

DUS NAMIDDAGS TK 4 UUR

DOOR

WILLEM VAALBURG

geboren te Castricum

Oriik: V.R.B.-Offset drukkerij - Kleine der A 4

Groningen — 1974.

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PROMOTORES: PROF. DR. M.G. WOLDRING

PROF. DR. H. WYNBERG

Page 45

Analysis.

The analysis of the irradiated gas was carried out on

a Packard 7400 gaschromatograph. The radioactivity of the

effluent gas of the thermal conductivity detector was

analysed with a lead-shielded Nal-scintillation detector,

a ratemeter and a recorder. The chromatography columns

used were:

a). H meter, £ inch stainless steel filled with 30-60

mesh activated charcoal (Chrompack, Holland).

Elution sequence N2, CO and CO2•

b). 4 meter, jj inch stainless steel filled with 80-100

mesh Poropak Q. Elution sequence N2 + CO, C02 •

The gaschromatograph was programmed, so that after

injection of the gas sample the temperature of the column

oven increased from 100 to 210 with a programmed rate

of 30 per minute and a final temperature holding period

of 5 minutes. Helium was used as carrier gas.

While the concentration of 1:iC0 and 11C02 in the

bombarded gas is ̂ too low to give a response of the

thermal conductivity detector, compound identification

was achieved by adding CO and CO2 as carrier to a 1 ml

sample of the bombarded gas, before injection on the

columns. In figure II.8.3. typical radiogaschromatograms

are given.

The 11C02 yield under different bombarding conditions

was determined by bubbling the activated gas during 5

minutes through 10 ml of a 1 N NaOH solution, fhe absorbed

radioactivity was measured in an ionisation chamber.

In table II.8.2. the radioactive composition of the

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Page 46

o

t

retention time (min.)
t I w 12 it

activated
charcoal

n

/
4 S t 10 12 M,

retention time (min.)

•o
o
o

• >

oa
c

•o

retention time (min.)

Nj+CO

ft 1

H 1
il i
" l
' i i
' l 1
i t j
1 t |
f i .

, J \j

Poropak 0

0
i
i
i

CO,

F\
1
1 V
1

1
1
1
\
1
\
V
\
\

u

2 3 4 5 6 7 »
retention time (min.)

Figure II.8.3, Radiogaschromatograms of the bombarded target gas.

Dashed line is the radioactivity distribution,

solid line the thermal conductivity of the

effluent gas.

bombarded gas and the ^CC^ yield under different

bombarding conditions are given. All the irradiations

were carried out with a beam spot of 1 cm2 and a target

gas flow of 500 ml/min.

Under a l l the irradiation conditions used the amount

of 11C0 was less than 1 % of the induced radioactivity

in the target gas. When the incident proton energy was

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Page 90

The short half-life makes particular demands on the whole

procedure. Since an upper limit of only three half-lives

of the radionuclide is available for the entire multi-

step procedure, high demands are made on the scientific,

technical and organisational skill of the entire team.

Obviously a major advantage of this rapid decay lies

m the possibility of readministration of the radio-

pharmaceutical and re-examination of the patient on the

same day.

The occurrence of the element carbon in nearly every

biological compound, the short half-life and the nuclear

properties of carbon-11 make the latter one of the most

useful radionuclides in Nuclear Medicine.

The aim of this investigation was the preparation of

some carbon-11 labelled amino acids and to test these

compounds as radiopharmaceuticals for pancreas

scintigraphy. Therefore we developed a new, rapid araino

acid synthesis based on the carboxylation of ct-lithio-

isocyanides with ^CC^, followed by hydrolysis of the

intermediate reaction product to the desired amino acid.

By this method DL-a-phenylalanine-1-11C was obtained >'

within 66 minutes and DL-a-phenylglycine-1-^C within

40 minutes. The chemical yields calculated with respect I

to the isocyanides were respectively 32 % and 78 %. •]

The 11CÜ2 used for the syntheses was prepared by a I

cyclotron with a yield of 1.5 mCi/yA.min via the nuclear 1

reaction lt+N (p. a) ^ C . A flow of nitrogen gas (mixed \
'i

with 0.1 % oxygen) was bombarded with 20 MeV protons at j

a target gas pressure of 3 atmospheres. The construction j

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Page 91

of the gas flow target system is described.

The carbon-11 labelled amino acids were administered

intravenously to rats and the distribution over pancreas,

liver, spleen, kidneys and blood was measured after

several time intervals. From these results the ratio of

the concentration in pancreas and liver was calculated

and compared with the corresponding figures from the

literature for some 18F-labelled aromatic amino acids

and with the data for L-selenomethionine-75Se. The

results point out that DL-a-phenylalanine-l-^C is better

suited and DL-a-phenylglycine-l-^C is less well suited

to pancreas scintigraphy than L-selenomethionine-75Se.

However from the data in the literature and from our

results we conclude that DL-6-fluorotryptophan-18F is

perhaps more suitable for visualisation of the pancreas

than DL-ot-phenylalanine-l-^C. The percentage of the

administered dose accumulating in the pancreas for both

amino acids is the same but the pancreas to liver ratio

for DL-6-fluorotryptophan-18F is higher than for DL-a-

This investigation indicates that the rapid synthesis

of organic compounds containing short-lived radionuclides

is feasable and that further developments in the synthesis

of organ specific organic radiopharmaceuticals can be

expected in the future.

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