ENGLISH ABSTRACT: Radiolabelled compounds have been widely used as investigative tools for
psychiatric disorders using positron emission tomography (PET) or single
photon emission tomography (SPECT) of the brain. In particular 123I-5-IR91150,
a serotonin (5-HT) 2a antagonist, has been used for imaging the
serotonergic system. The current study developed optimal radiolabelling and
purification methods in our laboratory with the objective that it can provide 123I-
5-I-R91150 in sufficient quantity and of acceptable pharmaceutical quality for
human use.
Unlabelled R91150 was obtained from Janssen Pharmaceutica (Beerse,
Belgium). Carrier free [123I]Iodine was produced by iThemba LABS, South
Africa, via the 127I(p,5n)123Xe-123I reaction, providing Na[123I] in 0.05 N sodium
hydroxide with a specific activity of 4000-6000 MBq/ml. A direct electrophilic
radioiodination method of labelling was used in this study for labelling 123-I-5-IR91150
in glacial acetic acid. After radiolabelling, the product was purified using
two different methods, namely a high performance liquid chromatography
(HPLC) purification method and a solid phase extraction (SPE) method. The
analyses of the purified product for both methods were done using HPLC.
Methods were tested to reduce the volume of the purified product using C8 or
C18 solid phase extraction cartridges.
The average labelling efficiencies for SPE and HPLC purification methods were
76% ± 13.6% and 52% ± 11.2% respectively. The yields of 123I-5-I-R91150 were
about 80%. Sep-Pak C8 and C18 were both unable to concentrate the HPLC
purified product. Products from both purification methods were sterile and
pyrogen free.
Both SPE and HPLC purification methods have been shown to provide products
meeting most criteria set for this study. However, both methods have
advantages and disadvantages. The SPE purification method provided higher
labelling efficiency and a much lower product volume. The stability of this
product is however of concern as some free iodide was detected. If this
purification method is used, the product should therefore be administered as
soon as possible after completion of analysis. After HPLC purification, the undiluted product remained stable up to 4.15 hours
after production but the product volume was relatively high, and purification
time-consuming. In order to obtain a useful patient dose, labelling would have to
start with at least 740 MBq 123I and the labelled product should be collected in
fractions of 5 ml or less in order to obtain a fraction of sufficiently high specific
activity.
It was concluded that radiolabeling R91150 is possible at our institution, but that
an improved HPLC system would be of value for routine production of a pure
and safe product.
AFRIKAANSE OPSOMMING: Radioaktief gemerkte verbindings word baie gebruik as ondersoekmiddel vir
psigiatriese afwykings met behulp van positron emissive tomografie (PET) of
enkelfoton emissie tomografie (SPECT) van die brein. Die verbinding 123I-5-IR91150,
‘n serotonien (5-HT) 2a antagonis, is beskryf vir beelding van die
serotonerge sisteem. Die huidige studie het ondersoek ingestel na optimale
metodes vir radioaktiewe merking en suiwering vir ons laboratorium met die
doel om 123I-5-I-R91150 in genoegsame hoeveelhed en van aanvaarbare
farmaseutiese gehalte geskik vir menslike gebruik te verskaf.
R91150 is van Janssen Pharmaceutica (Beerse, België) verkry. Draervry
[123I]jodium is deur iThemba LABS, Suid-Afrika, via die 127I(p,5n)123Xe-123I
reaksie geproduseer, om Na[123I] in 0.05 N natriumhidroksied met spesifieke
aktiwiteit van 4000-6000 MBq/ml te lewer. ‘n Direkte elektrofiliese
radioiodineringsmetode is in hierdie studie gebruik om 123-I-5-I-R91150 in
ysasynsuur te merk. Na radioaktiewe merking is die radioaktiewe produk deur
twee verskillende metodes gesuiwer, naamlik ‘n HPLC metode en ‘n soliede
fase ekstraksie (SPE) metode. Vir beide metodes is die produk deur middel van
HPLC analiseer. Metodes is getoets om die volume van die gemerkte produk
met C8 of C18 SPE kolommetjies te verminder.
Die gemiddelde bindingsdoeltreffendheid vir die SPE en HPLC
suiweringsmetodes was 76% ± 13.6% en 52% ± 11.2% onderskeidelik. Die
opbrengs van 123I-5-I-R91150 was ongeveer 80%. Sep-Pak C8 en C18 kon
beide nie gebruik word om die HPLC gesuiwerde produk te konsentreer nie.
Produkte van beide suiweringsmetodes was steriel en pirogeenvry.
Daar is getoon dat beide suiweringsmetodes produkte lewer wat aan die
meeste kriteria wat in hierdie studie gestel is, voldoen. Beide metodes het egter
voor- en nadele. Die SPE suiweringsmetdode het tot hoër
bindingsdoeltreffendheid gelei, asook ‘n baie laer produkvolume. Daar is egter
‘n mate van kommer oor die stabiliteit van die produk aangesien vry radiojodied
waargeneem is. Indien hierdie suiweringsmetode gebruik word, moet die produk
dus so gou as moontlik na voltooiing van analise toegedien word.
Na HPLC suiwering was die onverdunde produk tot 4.15 uur na produksie
stabiel maar die produkvolume was relatief hoog en suiwering tydrowend. Om ‘n bruikbare pasiëntdosis te verkry moet merking met ten minste 740 MBq 123I
begin en die gemerkte produk moet na suiwering in fraksies van 5 ml of minder
versamel word om ‘n fraksie met geskikte spesifieke aktiwiteit te verkry.
Die gevolgtrekking is gemaak dat radioaktiewe merking van R91150 by ons
instelling moontlik is, maar dat ‘n verbeterde HPLC sisteem vir roetineproduksie
van ‘n suiwer en veilige produk van waarde sou wees.
