TY - JOUR
T1 - Synthesis and in vivo evaluation of 122I- and 131I-labelled iodoperidol, a potential agent for the tomographic assessment of cerebral perfusion
AU - Moerlein, Stephen M.
AU - Mathis, Chester A.
AU - Brennan, Kathleen M.
AU - Budinger, Thomas F.
N1 - Funding Information:
blood concentrations of these radiolabelled neu-brain/muscleconcentrationratioof 7.0 found in the rolepticsa rel istedi n Table 2 along with their relative rat (Table 1). Figure 1 also suggesttshatpreferential brain/blood concentrationr atios,m olecularw eights, accumulation of [‘221]IPin the more highly per-and octanol-water partition coefficients.I t can be fusedgreymatterof the brain takesplace,although seen from this table that as the lipophilicity of the the resolution of the tomograph (8 mm FWHM neuroleptici s increasedt,h e brain and blood concen-(Derenzo et al., 1981))limits the clear distinction trationsp asst hrougha maximumv aluef or [77Br]BP. betweengreyand white matterin the dogbrain. The relativelyl ower cerebralu ptakea nd blood con-centrationf ound with [‘3’I]IP may be duet o enhanced nonspecificb inding of the more lipophilic IP compound to lipoidal siteso f extravasculare,x tracerebral tissues.I n addition, the higher molecularw eightof this analoguem ay also hinder its diffusion acrosst he blood-brain barrier( BBB). Similar relationshipsh ave beenn otedb etweenli pophilicity and theb rain uptake of 77Br-labellesdp iperonea nalogues (Moerleeitn a l., 1985b)o r “C-labelled compounds( Dischino et al., 1983). The maximum brain extraction shown in Table 2 correspondst o a log P value of 2.4, which agreesc losely with the log P of 2.5 predictedf or optimum permeationo f the BBB by neutral radiopharmaceutical(sD ischino et al., 1983).T he data in Table 2 also indicate that thec erebralu ptakeo f IP may be improvedb y chemicallym odifying the radio-iodinated compound so thati ts lipophilicity more Acknowledgements-The authorst hankP rofessorG . Stock- closely approximatesth at of BP. Such modification F.R.G., for stimulatingd iscussionsW. e also acknowledge lin of the KernforschungsanlagJeii lich GmbH., Jiilich, should be possiblew ithout exceedingth e molecular the assistanceof Y. Yano and M. Singh in the experiments weight limit of about 550 dalton at which BBB involving* *R b, and M. S. Lagunas-Solaar nd D. Manthei permeationb egins to decrease(L evin, 1980). of Cracker NucleaLra boratory,University of California Although the in vivo characteristicos f IP are not This work was supportedi n part by the Director, Office at Davis, for the preparationa nd shipmento f ‘22Xeg as. ideal for a flow marker, this butyrophenonen euro-of Energy Research,O ffice of Health and Environmental leptic nonethelesss hows potential as an agent for Research,B iology and Medicine Division of the U.S. measuring cerebral perfusion. This is particularly Departmento f Energy under Contract No. DE-AC03- true when ‘**I is used as a label for PET imaging, 76SFOOO9a8n d grants from the National Institutes of since the shorth alf-life of this generator-produced RR05918. Health ROI NS22899, PO1 HL25840 and BRSG SO7 radionuclide eliminatesc oncern for high absorbed radiation doses,e speciallyt hat to the thyroid which would occur if the iodine had a longer half-life. The data in Table 1 indicate that thec erebral uptake,c erebralr etention,a nd blood clearancea re sufficientlyg reatat short intervals post injection to warrant applicationo f ‘22It o this classo f agents.A s illustrated in Figs 1 and 2, thei n vivo pharmacokinetics of [‘221]IP allowv isualization of perfused areaso f the brain with PET. There is relativelyh igh brain uptake,p racticallyc ompletere tentiona, nd great specificityf or cerebral tissue by [‘221]IP.F igure 2 indicatesa brain/soft tissue concentrationr atio of 5.1 for [‘221]IPin the dogi,n good agreemenwt ith the
PY - 1987
Y1 - 1987
N2 - Iodoperidol (IP), an iodinated analogue of the antipsychotic drug haloperiodol, was evaluated as a cerebral blood flow radiopharmaceutical for PET or SPECT. IP was labelled with 131I or 122I (76% β+, t 1 2 = 3.6 min) in >75% radiochemical yield via electrophilic aromatic iododestannylation. [131I]IP showed high cerebral uptake (1.9% of injected dose after 5 min) and good brain retention for the rat, with very low blood levels (brain/blood ratio = 35 at 2 h post injection). PET imaging of a dog demonstrated that [122I]IP has high selectivity for brain localization and good retention, and indicates that this class of compounds holds promise for development as perfusion radiopharmaceuticals.
AB - Iodoperidol (IP), an iodinated analogue of the antipsychotic drug haloperiodol, was evaluated as a cerebral blood flow radiopharmaceutical for PET or SPECT. IP was labelled with 131I or 122I (76% β+, t 1 2 = 3.6 min) in >75% radiochemical yield via electrophilic aromatic iododestannylation. [131I]IP showed high cerebral uptake (1.9% of injected dose after 5 min) and good brain retention for the rat, with very low blood levels (brain/blood ratio = 35 at 2 h post injection). PET imaging of a dog demonstrated that [122I]IP has high selectivity for brain localization and good retention, and indicates that this class of compounds holds promise for development as perfusion radiopharmaceuticals.
UR - http://www.scopus.com/inward/record.url?scp=45949130886&partnerID=8YFLogxK
U2 - 10.1016/0883-2897(87)90137-1
DO - 10.1016/0883-2897(87)90137-1
M3 - Article
AN - SCOPUS:45949130886
SN - 0883-2897
VL - 14
SP - 91-93,95-98
JO - International Journal of Radiation Applications and Instrumentation.
JF - International Journal of Radiation Applications and Instrumentation.
IS - 2
ER -