HPLC investigation of preparation variables on the radiochemical purity of 99mTc-MIBI

HPLC INVESTIGATION OF

PREPARATION VARIABLES ON THE

RADIOCHEMICAL PURITY OF

Tc-MIBI

Dr. BETÜL TAŞDELEN, NUR SAYGI, HÜLYA YILDIZ

TAEK

Technetium-99m

(

Tc)

is the most

widely used

radionuclide in

clinical nuclear

medicine for

WHY

Tc IS THE FAVOURED CHOICE

OF THE MEDICAL PROFESSION ?

Its half life is

six hours

,

-Long enough for a medical

examination

-Short enough to allow a

patient to leave the hospital soon

afterwards.

99m

Tc is generated

from

Mo

, which has

a half-life of

66 hours

,

allowing it to be

transported over fairly

long distances.

Technetium-99m (

Tc)

Ideal physical characteristics

 Short physical half-life (T_1/2) of 6 h;   energy of 140 keV;

 No particulate emission during decay

Ideal chemical properties

 99mTc easily combines with a large number

of ligands

99m

Tc is used in

20 million

diagnostic

nuclear

medical

procedures,

Bone scans (half of them)

The other half are roughly divided

between

kidney, heart and lung

scans.

Approximately

85

percent

of diagnostic

imaging procedures in

nuclear medicine use this

isotope.

The agents for measurement of cardiac

perfusion include:

99m

Tc-MIBI (Cardiolite, DuPont-Merck

Pharm. Co., Inc)

99m

Tc-tetrofosmin (Myoview, Amersham

Measurement of cardiac

perfusion with

Tc-MIBI is

widely used in clinical

nuclear medicine for the

diagnosis of coronary artery

disease.

In addition,

Tc-MIBI has

been shown to be useful in

identifying several types of

tumors

, such as breast, lung

and thyroid cancers.

99m

Tc-MIBI (Cardiolite) is to

be used with

25-150 mCi

(0.92-5.55 GBq) of

The Pharmacopoeia for

99m

Tc-MIBI recommends at

least 90% radiochemical

Various factors may influence

the RCP of certain reagent kits

Some of these include:

the amount of activity added to the

reagent kit,

heating time and temperature,

the eluate age,

THE AIM OF THIS WORK

The effect of these factors on

RCP of

Tc-MIBI has been

investigated using an

SUMMARY OF OUR STUDY

Formulation of kit for

Tc-MIBI

Radiolabelling of

Tc-MIBI

Radiochemical Quality Control of

Formulation of kit

for

99m

Tc-MIBI

Sodium citrate dehydrate

MIBI

L-cysteine

Mannitol

Radiolabelling of

Tc-MIBI

The standard

Tc-MIBI was prepared

by addition of generator eluate

Tc to

the prepared kit vial and

heating for 10

min

in a boiling water bath.

Preparations were allowed to

cool for

15 mins

.

RADIO-HPLC

Agilent Quaternary Pump with Degasser Manual Injector

HPLC Column C-18 (4.6 mm x 250 mm)

2 x2" NaI(Tl) scintillation detector (GABI Star flow cell)

GABI Star gamma flow monitor with GINA Star program

HPLC Chromatogram of 99mTcO 4- (10 mCi (370 MBq)) Ch1 20 30 40 50 60 70 80 90 100 110 CPS *1000 T c O 4

-HPLC Chromatogram of 99mTc-MIBI

(low activity; 25 mCi (0.92 GBq), 99.0% RCP) Ch1 50 100 150 200 250 300 CPS *1000 T c 9 9 m -M I B I

HPLC Chromatogram of

Tc-MIBI

(high activity; 50 mCi (1.84 GBq), 96.18% RCP) Ch1 150 200 250 300 350 400 450 CPS *1000 T c 9 9 m -M I B I

HPLC chromatogram of 99mTc-MIBI without heating (25 mCi (0.92 GBq), 49.82%) Ch1 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 CPS *1000 6 . 9 7 . 1 7 . 5

We also used ITLC-SG technique in order to determine the RCP of 99mTc-MIBI.

ITLC-SG developed in two solvent systems (acetone/saline).

ITLC-SG strips developed with saline to determine 99mTc pertechnetate and with

acetone to determine 99mTc colloid; %99m

Tc-MIBI was determined by difference from 100%.

Radiochemical purity of

Tc-MIBI

ITLC-SG (R_f of species)

SOLVENT 99mTc-MIBI 99TcO

4- Red. 99mTc

Acetone 0.5-1 0.35-1 0-0.25

Normal

The RCP was assessed by HPLC

and ITLC-SG, immediately and

1-5 h after reconstitution of the

99m

Tc-MIBI.

It was found that the freeze-dried

kit for

Tc-MIBI of high

HPLC Chromatogram of

Tc-MIBI

25 mCi (0.92 GBq), 95.72% RCP,

HEATING TIME

We have also investigated the effect of

heating time on RCP.

After the addition of 3 mL generator eluate

containing 25 mCi

Tc to each kit vial

and they were heated for either

10 min,

20

and

30 min

in a boiling water bath.

Table 1. The effect of the heating time on

RCP (activity, 25 mCi (0.92 MBq))

Run No Heating Time

(min) _{RCP (%)}HPLC

1 10 99.00

2 20 99.13

Table 2. The effect of the eluate age on

RCP (activity, 25 mCi (0.92 MBq))

Run No Eluate Age (hour)

HPLC RCP (%)

1 0 99.00

CONCLUSION

99m

Tc-MIBI is a promising

Tc-labeled

radiopharmaceutical

for

myocardial imaging.

99m

Tc-MIBI must be rapidly available

to permit administration

without

any

That is why we selected

HPLC

and

ITLC-SG

methods and these methods

take

10

and

3 min

, respectively. They

are

faster

and

more reliable

methods

for the analysis of radiochemical

purity of

Tc-MIBI.

RCP tests of

Tc-MIBI kits in our