open access

Vol 15, No 2 (2012)
Original articles
Published online: 2012-08-30
Submitted: 2012-08-31
Accepted: 2012-08-31
Get Citation

Comparison of chromatographic methods for quality control of DMSA complexes with 99mTc and 188Re at (III) and (V) oxidation states

Piotr Garnuszek, Dariusz Pawlak, Michał Maurin, Drina Jankovic, Urszula Karczmarczyk, Renata Mikołajczak
Nucl. Med. Rev 2012;15(2):95-100.

open access

Vol 15, No 2 (2012)
Original articles
Published online: 2012-08-30
Submitted: 2012-08-31
Accepted: 2012-08-31

Abstract

BACKGROUND: The reliable method for determination of
identity and radiochemical purity (RCP) is of great importance
in radiopharmaceutical development. This is especially relevant
when more than one form of radiometal/ligand complex can be
formed during radiolabelling, such as complexes of 99mTc or 188Re
with meso-2,3-dimercaptosuccinic acid (DMSA), where depending
on the pH, metal can occur either at +3 or +5 oxidation state.
The aim of our study was to evaluate possibilities for optimization
of chromatographic systems leading to specific and reliable
analytical method for determination of the identity and RCP of
DMSA complexes with 99mTc or 188Re.


MATERIAL AND METHODS: The commercial DMSA kits
(POLATOM) were used for preparation of technetium-99m (III) and (V) complexes with DMSA. 99mTc(V)-DMSA complexes
were prepared by addition of NaHCO3 to the kit vial prior to
99mTc-eluate to obtain pH ~8. 188Re(V)-DMSA was prepared either
directly or using intermediate 188Re(III)-EDTA complex added
to DMSA. RCP was evaluated by TLC using: ITLC-SG developed
in methylethylketon, SG60 coated plates developed in:
n-BuOH/H2O/CH3COOH and n-PrOH/H2O/CH3COOH systems,
and in H2O. Comparative biodistribution studies were performed
in normal Wistar rats.


RESULTS: Using silica gel plates and n-PrOH, H2O and acetic
acid in the developing solution, we observed that 99mTc/188Re(III)-
DMSA and 99mTc/188Re(V)-DMSA complexes could be well
separated from each other and from the impurities in the form
of free pertechnetate/perrhenate. In vivo studies showed quite
different biodistribution of 99mTc(III)- and 99mTc(V)-DMSA. The
trivalent complex accumulated mainly in kidneys (>40%ID),
while 99mTc(V)-DMSA revealed high excretion with urine and
relatively high concentration in osseous tissue (ca. 2 %ID/g).
Accumulation of this complex in kidneys was very low (ca.
2.5 %ID). Biodistribution pattern of 188Re(V)-DMSA prepared
directly was almost identical to that of 99mTc(V)-DMSA. Biodistribution
results of the 188Re preparation obtained using 188Re(III)-
EDTA intermediate indicated that the preparation contained the
mixture of penta- and trivalent 188Re complexes. The quite high
accumulation of radioactivity in kidneys (23 %ID) gave evidence
of the presence of 188Re(III)-DMSA in this preparation, what was
also confirmed by the results of TLC analysis performed using
silica gel plate and n-propanol/water/acetic acid as developing
system.

CONCLUSIONS: Based on our study, we have made recommendation
on the suitable methods for investigations of RCP of
DMSA complexes, i.e.: SG60 plates developed in the mixture
of n-propanol/water/acetic acid, which enable determination of the tri- and pentavalent DMSA complexes, as well as, the
pertechnetate/perrhenate impurity, and developed in water for
determination of the colloidal residue.

Abstract

BACKGROUND: The reliable method for determination of
identity and radiochemical purity (RCP) is of great importance
in radiopharmaceutical development. This is especially relevant
when more than one form of radiometal/ligand complex can be
formed during radiolabelling, such as complexes of 99mTc or 188Re
with meso-2,3-dimercaptosuccinic acid (DMSA), where depending
on the pH, metal can occur either at +3 or +5 oxidation state.
The aim of our study was to evaluate possibilities for optimization
of chromatographic systems leading to specific and reliable
analytical method for determination of the identity and RCP of
DMSA complexes with 99mTc or 188Re.


MATERIAL AND METHODS: The commercial DMSA kits
(POLATOM) were used for preparation of technetium-99m (III) and (V) complexes with DMSA. 99mTc(V)-DMSA complexes
were prepared by addition of NaHCO3 to the kit vial prior to
99mTc-eluate to obtain pH ~8. 188Re(V)-DMSA was prepared either
directly or using intermediate 188Re(III)-EDTA complex added
to DMSA. RCP was evaluated by TLC using: ITLC-SG developed
in methylethylketon, SG60 coated plates developed in:
n-BuOH/H2O/CH3COOH and n-PrOH/H2O/CH3COOH systems,
and in H2O. Comparative biodistribution studies were performed
in normal Wistar rats.


RESULTS: Using silica gel plates and n-PrOH, H2O and acetic
acid in the developing solution, we observed that 99mTc/188Re(III)-
DMSA and 99mTc/188Re(V)-DMSA complexes could be well
separated from each other and from the impurities in the form
of free pertechnetate/perrhenate. In vivo studies showed quite
different biodistribution of 99mTc(III)- and 99mTc(V)-DMSA. The
trivalent complex accumulated mainly in kidneys (>40%ID),
while 99mTc(V)-DMSA revealed high excretion with urine and
relatively high concentration in osseous tissue (ca. 2 %ID/g).
Accumulation of this complex in kidneys was very low (ca.
2.5 %ID). Biodistribution pattern of 188Re(V)-DMSA prepared
directly was almost identical to that of 99mTc(V)-DMSA. Biodistribution
results of the 188Re preparation obtained using 188Re(III)-
EDTA intermediate indicated that the preparation contained the
mixture of penta- and trivalent 188Re complexes. The quite high
accumulation of radioactivity in kidneys (23 %ID) gave evidence
of the presence of 188Re(III)-DMSA in this preparation, what was
also confirmed by the results of TLC analysis performed using
silica gel plate and n-propanol/water/acetic acid as developing
system.

CONCLUSIONS: Based on our study, we have made recommendation
on the suitable methods for investigations of RCP of
DMSA complexes, i.e.: SG60 plates developed in the mixture
of n-propanol/water/acetic acid, which enable determination of the tri- and pentavalent DMSA complexes, as well as, the
pertechnetate/perrhenate impurity, and developed in water for
determination of the colloidal residue.

Get Citation

Keywords

meso-2,3-dimercaptosuccinic acid (DMSA), 99mTc(III) and (V), 188Re(V), complexes, identity, radiochemical purity, radiochromatography

About this article
Title

Comparison of chromatographic methods for quality control of DMSA complexes with 99mTc and 188Re at (III) and (V) oxidation states

Journal

Nuclear Medicine Review

Issue

Vol 15, No 2 (2012)

Pages

95-100

Published online

2012-08-30

Bibliographic record

Nucl. Med. Rev 2012;15(2):95-100.

Keywords

meso-2
3-dimercaptosuccinic acid (DMSA)
99mTc(III) and (V)
188Re(V)
complexes
identity
radiochemical purity
radiochromatography

Authors

Piotr Garnuszek
Dariusz Pawlak
Michał Maurin
Drina Jankovic
Urszula Karczmarczyk
Renata Mikołajczak

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., Świętokrzyska 73 street, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl