In vivo binding in rat brain and radiopharmaceutical preparation of radioiodinated HEAT, an alpha-1 adrenoceptor ligand

In vivo binding of [125I]-2-[beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ([125I]HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of [125I]HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of [125I]HEAT is saturable. At 4 hr, [125I]HEAT or [123I]HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and [125I]HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.     

In vivo SPECT imaging of CNS D-2 dopamine receptors: initial studies with iodine-123-IBZM in humans

Iodobenzamide (IBZM) is a D-2 dopamine receptor antagonist. In this paper the results of Phase I clinical studies of iodine-123-(123I)IBZM in humans are reported. Preliminary imaging studies, both planar and single-photon emission tomography (SPECT), of no-carrier added [123I]IBZM in humans show specific localization in the basal ganglia of the brain. At 2 hr after an i.v. injection, the brain uptake was 3.72% of the dose, and at 20 hr later the uptake diminished to 0.7%. Radiation dosimetry calculation indicated that the radiation dose to the brain was minimum, 0.039 rad/mCi, while the large intestine wall received the highest dose, 0.28 mrad/mCi. The radiation dosimetry and pharmacology data suggest that this agent is safe for human use.     

Biodistribution and radiation dosimetry of radioiodinated-SCH 23982, a potential dopamine D-1 receptor imaging agent

Radioiodinated-SCH 23982 is a potential agent for the imaging of dopamine D-1 receptors in the human brain. In vivo binding of [125I]SCH 23982 to D-1 receptors in rat brain was determined over 4 hr. The ratio of activity in striatum and frontal cortex to that in cerebellum increased over the first 2 hr to maximum values of 4.4:1 and 2.1:1, respectively. The percent injected dose in whole brain at 0.5 and 2 hr were 0.62 and 0.15, respectively. Administration of the antagonists propranolol (beta-1), prazosin (alpha-1), haloperidol (D-2) and ketanserin (5HT-2) did not significantly alter the striatum/cerebellum ratio; however, SCH 23390, a D-1 antagonist, totally blocked ligand uptake by striatum and frontal cortex. Biologic distribution data in the rat were determined after injection of 3 microCi of [125I]SCH 23982. 76% of the injected dose was excreted in 48 hr via the liver and kidneys. Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads and red bone marrow were calculated for humans using the physical decay data for 123I. The critical organ was found to be the lower large intestine which received 1.1 rad/mCi of the administered dose. The total-body dose was 63 mrad/mCi. The data indicate that [123I]SCH 23982 should be a suitable agent for imaging the D-1 dopamine receptor in the human brain by single photon emission computed tomography.     

Biodistribution and dosimetry of N-isopropyl-p-[123I]iodoamphetamine in the primate

The biodistribution of N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) in the Macaca fascicularis monkey was determined at 15 min and at 1, 4, 24, and 48 hr after intravenous injection. Brain uptake was 7.8% of the injected dose at 1 hr, with little change in concentration between 15 min and 1 hr, falling thereafter. Eye uptake reached a maximum of 0.23% of injected dose at 24 hr, with activity primarily in the pigmented layers. The human absorbed radiation dose was calculated on the basis of biodistribution data. The critical organ is the eye (0.407 rad/mCi of I-123 IMP). The eye dose increased to 1.11 rad/mCi with 4% contamination from I-124 IMP and to 0.535 rad/mCi with 0.4% contamination from I-125 IMP. The absorbed dose to the liver was 0.127 rad/mCi for pure I-123 IMP and the thyroid dose was 0.120 rad/mCi, both increasing with either I-124 or I-125 contamination. While delayed eye uptake has not yet been reported in the human, care should be exercised in limiting the amount of contaminating I-124 or I-125 to the lowest practical level.     

Radiosynthesis and preliminary evaluation of 5-[123/125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine: a radioligand for nicotinic acetylcholine receptors

The radiochemical syntheses of 5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5-[123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)metho xy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/mumol, respectively. Binding affinities of [125I]1 and [123I]1 in vitro (rat brain membranes) were each characterized by a Kd value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.     

Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons.

The central nervous system dopamine transporters (DATs) and dopamine D2/D3 receptors are implicated in a variety of neurological disorders. Both sites are also targets for drug treatment. With the successful development of [99mTc]TRODAT-1, single-isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of 123I-labeled D2/D3 receptor ligand co-injected to assess both pre- and postsynaptic sites of the dopaminergic system simultaneously. METHODS: Twelve SPECT scans of the brain were obtained in two baboons after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl ](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [123I]iodobenzamide or [123I]iodobenzofuran. SPECT data were acquired by a triple-head gamma camera equipped with ultra-high-resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10% asymmetric with a lower bound at 159 keV for 123I. After coregistration with MRI, region-of-interest analysis was performed using predefined templates from coregistered MRI. In blocking studies, baboons were pretreated with N-methyl-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D2/D3 binding site, respectively. RESULTS: Image quality of dual-isotope studies was similar to that obtained from single-isotope studies. When one site was blocked with CFT or raclopride, the binding of the respective ligand to the other site was not affected. CONCLUSION: This is the first example that clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic sites of the dopaminergic system in baboons with dual-isotope SPECT studies. With or without corrections for cross-contamination of 123I into the 99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual-isotope experiments did not differ significantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopaminergic system in one SPECT imaging session.     

Synthesis of an I-123 analog of A-85380 and preliminary SPECT imaging of nicotinic receptors in baboon

A radiosynthetic method to prepare the nicotinic acetylcholine receptor radioligand (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine, 5-IA, has been developed. The two-step sequence produced [123I]-5-IA in high radiochemical yield (52%), high radiochemical purity (98%), and high specific radioactivities (> 8,500 mCi/mumol). Preliminary single photon emission computed tomography studies with [123I]-5-IA in baboon demonstrated the appropriate regional localization for a high-affinity nicotinic radioprobe (thalamus > frontal cortex > cerebellum). Pretreatment with cytisine blocked [123I]-5-IA uptake in all brain regions (78-59% reduction), demonstrating the specificity of the radiotracer.     

Imaging serotonin and dopamine transporters with 123I-beta-CIT SPECT: binding kinetics and effects of normal aging.

[123I]beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (CIT) is a useful ligand for dopamine transporters (DATs) and serotonin transporters (5-HTTs). Previous SPECT studies have shown a state of sustained equilibrium in the striatum on day 2 after injection that allows quantification of striatal DATs using a simple ratio of specific-to-nondisplaceable binding. The aim of this study was to investigate the kinetics of [123I]beta-CIT uptake in the thalamus, hypothalamus, and midbrain, areas known to contain 5-HTTs in high densities. METHODS: SPECT with a triple-head camera was performed on 16 healthy volunteers (13 women, 3 men; mean age [+/-SD], 32 +/- 11 y) after intravenous bolus injection of 130 +/- 20 MBq (3.5 +/- 0.5 mCi) [123I]beta-CIT. Two individuals were scanned 1, 2, 4, 7, 10, 13, 16, and 24 h after injection, and the remaining 14 were scanned 4, 7, 10, 20, and 24 h after injection. Values from 19 previously examined healthy volunteers (8 women, 11 men; mean age, 52 +/- 20 y) were included in the analysis to study the age dependency of beta-CIT binding in striatal and 5-HTT-rich brain areas in a larger control sample. RESULTS: Peak uptake 4 h after injection, followed by stable uptake until 10 h and a slow decrease until 24 h, was observed in the thalamus-hypothalamus region. Activity in the midbrain-pons region peaked 2 h after injection. Because of a concomitant slow but steady decline of uptake in reference regions starting 4 h after injection, a higher stability of binding ratios for 5-HTT-rich brain areas was observed on day 2, suggesting that a state of transient equilibrium is reached between 20 and 24 h but that conditions are only close to transient equilibrium between 4 and 10 h after injection for 5-HTT-rich brain areas. In addition to an age-related decline of striatal [123I]beta-CIT binding of 6.6% per decade, a significant age-associated decrease of beta-CIT binding of 3-4% per decade was found in 5-HTT-rich brain areas. The decline of beta-CIT binding in these regions may be explained, at least in part, by a loss of monoamine transporters with age but may also be related to age-associated morphologic changes. CONCLUSION: [123I]beta-CIT appears to be a suitable ligand for imaging serotonin transporters with SPECT. However, careful age matching is warranted for [123I]beta-CIT SPECT studies of 5-HTT changes in patients with neuropsychiatric disorders.     

Thallium-201 diethyldithiocarbamate: an alternative to iodine-123 N-isopropyl-p-iodoamphetamine

The study of cerebral blood flow by single photon emission computed tomography (SPECT) requires lipophilic radiopharmaceuticals. The high cost and limited availability of N-isopropyl-p-[I-123]-iodoamphetamine ( [123I]IMP) led us to search for alternatives. Following our recent development of thallium-201 diethyldithiocarbamate ( [201TI]DDC), we have compared the brain uptake of [123I]IMP and [201TI]DDC in rabbits. The brain bound 1.14 +/- 0.28% (s.e.m.) of the dose of the injected [123I]IMP and 1.46 +/- 0.28% of the [201TI]DDC. Brain activity of [201TI]DDC remained stable from 1.5 min after injection up to at least 1 hr. The [201TI]DDC uptake was more instantaneous than that of [123I]IMP. The ratios of gray to white matter distribution were about equal: 1.41 for [123I]IMP and 1.44 for [201TI]DDC. The lungs retained 8.32% of the dose of [123I]IMP and only 0.53% of the [201TI]DDC. In brain macroautoradiography [201TI]DDC yielded images of good quality with excellent demarcation of gray and white matter, persisting for at least 45 min after injection. We conclude that [123I]IMP and [201TI]DDC are equally suitable for blood flow study of the rabbit brain. The first human tomographic results obtained in two healthy volunteers demonstrate that clinical application of SPECT [201TI]DDC may be feasible.     

Effects of ageing on serotonin transporters in healthy females

The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [123I]nor-beta-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [123I]nor-beta-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [123I]nor-beta-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade).     

5-[<Superscript>123</Superscript>I]Iodo-A-85380: assessment of pharmacological safety,radiation dosimetry and SPECT imaging of brain nicotinic receptors in healthy human subjects

Recently, 5-[123I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([123I]5IA) was developed as a ligand for imaging the nicotinic acetylcholine receptor (nAChR) in human brain using single photon emission computed tomography (SPECT). In the present study, the toxicity and radiation absorbed dose of [123I]5IA were investigated. Behavior and physiological parameters were examined in mice and rats after administration of 5IA. There were no changes in these parameters in animals administered 1 microg/kg of 5IA or less, indicating that the no observed effect level (NOEL) of 5IA was 1 microg/kg. [123I]5IA was then administered to healthy human subjects and serial whole-body images were acquired over 24 hr. Initially, high levels of radioactivity were observed in the liver and urinary bladder and moderate levels in the lungs, kidneys, and brain. Whole brain activity at 1 hr was 4.6 +/- 0.4% of the injected dose and this value gradually decreased with time. The majority (-75%) of the radioactivity was excreted in urine within 24 hr, and less than 1% remained in all organs tested. The biological half-life of [1231]51A averaged 7.2 +/- 4.0 hr. Based on the biodistribution data, radiation absorbed doses were estimated using MIRDOSE 3.1 software with the dynamic bladder model and the ICRP gastrointestinal (GI) tract model. Consequently, the effective dose equivalent was estimated to be 30 +/- 1.4 microSv/MBq, which is an acceptable radiation burden. Having determined the safety of this compound, we performed SPECT imaging in a healthy human subject using 171 MBq of [123I]5IA. SPECT images clearly revealed a cerebral distribution of radioactivity that was consistent with the known distribution of central nAChRs in humans. These results suggest that [123I]5IA is a promising ligand for imaging nAChRs in humans, with an acceptable dosimetry and pharmacological safety at the dose required for adequate SPECT imaging.     

Quantitative evaluation of iodine-123 hippuran gamma camera renography in normal children

In a retrospective study of 39 normal children submitted to [123I]hippuran gamma camera renography, a quantitative evaluation of the recorded data showed that: (a) the rate constant for renal plasma clearance of [123I]hippuran was -0.166 +/- 0.043 min-1 corresponding to a hippuran plasma clearance of 518 +/- 142 ml/min per 1.73 m2; (b) the fractional renal clearance of [123I]hippuran was 0.51 +/- 0.03 and 0.49 +/- 0.03 for the left and the right kidney, respectively; and (c) the mean values for the mean transit times of [123I]hippuran through the whole kidney, the renal parenchyma, and the renal pelvis, respectively, were 4.2, 1.9, and 2.5 min. Five kidneys (in four patients) showed prolonged renal mean transit times of [123I]hippuran. Follow-up renographies were performed in three of the four children and gave normal results. Patients with renal mean transit times above the present 5% significance limit of 8.2 min should not necessarily be considered having an abnormal renal function.     

Radiation dosimetry from breast milk excretion of radioiodine and pertechnetate

Measurements were made of the activity in samples of breast milk obtained from a patient with postpartum thyroiditis following administration of [123I]sodium iodide and subsequently [99mTc]pertechnetate 24 hr later. Both 123I and 99mTc were found to be excreted exponentially with an effective half-life of 5.8 hr and 2.8 hr, respectively. Less than 10% of the activity was incorporated into breast-milk protein. After administration of [123I]sodium iodide breast feeding should be discontinued for 24-36 hr to reduce the absorbed dose to the child's thyroid.     

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.     

Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma

The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of 123I activity in the brain after [123I]5-IA administration can be interpreted as distribution of an intact radiotracer.     

In vivo evaluation of [(123)I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one: a presumed dopamine D4 receptor ligand for SPECT studies

[(123)I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one ([(123)I]-ITCP), a presumed radioligand for visualization of the dopamine D4 receptor by single photon emission computed tomography, was evaluated in vivo in mice and rabbits. This new radioiodinated tracer exhibited high brain uptake (3.64% injected dose per gram of tissue at 10 min p.i.) in mice. No significant amounts (less than 5%) of labeled metabolites were present in the brain, as demonstrated by a metabolite study. Regional brain distribution in rabbits showed atypical CNS uptake with consistently low values in the cortex and high values in other brain parts including cerebellum. Saturable binding was confirmed by a competition experiment with unlabeled product. Selectivity was assessed by competition experiments with a known dopamine D4 ligand and later with a sigma receptor ligand. Both experiments showed no observable competition. In conclusion, our findings indicate that [(123)I]-ITCP is neither a dopamine D4 receptor ligand nor a sigma receptor ligand. The exact nature of [(123)I]-ITCP binding in the brain remains to be elucidated.     

Effects of ageing on serotonin transporters in healthy females

The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [¹²³I]nor-#-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [¹²³I]nor-#-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [¹²³I]nor-#-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade).     

High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation.

Thirty-two patients with multiple myeloma were treated with high doses of 166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid (DOTMP) and were a subset of patients enrolled in a multicenter phase I/II dose escalation myeloablative trial. 166Ho with beta-emission (half-life, 26.8 h; beta-particle energies, 1.85 MeV [51%] and 1.77 MeV [48%]; gamma-photons, 80.6 keV [6.6%] and 1.38 MeV [0.9%]) was complexed to DOTMP, a macrocyclic tetraphosphonate. Pharmacokinetics, dosimetry, and biodistribution were studied. METHODS: Patients were treated at escalating dose levels of 20, 30, and 40 Gy to the bone marrow in combination with high-dose melphalan, with or without total-body irradiation, to evaluate toxicity and efficacy. After infusion with 1,110 MBq (30 mCi) of 166Ho-DOTMP for evaluation of biodistribution and dosimetry calculation, patients received the calculated amount of radioactivity for therapy in a single administration based on estimated dose calculations. RESULTS: Thirty-two patients participated in the study and were then treated. The average amount of administered radioactivity was 74.3 GBq (2,007 mCi) (range, 21.5-147.5 GBq [581-3,987 mCi]) of 166Ho-DOTMP. CONCLUSION: 166Ho-DOTMP has physical and pharmacokinetic characteristics compatible with high-dose myeloablative treatment of multiple myeloma.     

Biodistribution and radiation dosimetry of [<Superscript>123</Superscript>I]ADAM in healthy human subjects: preliminary results

[(123)I]ADAM [2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM)] has recently been shown to be a very promising imaging ligand for the detection of serotonin transporters (SERT) in human brain, because of its high specificity for SERT. [(123)I]ADAM has previously been used only for animal studies. In this work, we investigated the radiation dosimetry and biodistribution of [(123)I]ADAM based on whole-body scans in healthy human volunteers. Following the administration of 196+/-20 MBq (range 157-220 MBq) [(123)I]ADAM, serial whole-body images were performed up to 24 h. Estimates of radiation absorbed dose were calculated using the MIRDOSE 3.0 program with a dynamic bladder model. Twelve source organs were considered in estimating absorbed radiation doses for organs of the body. The highest absorbed organ doses were found to the lower large intestine wall (8.3.10(-2) mGy/MBq), kidneys (5.2.10(-2) mGy/MBq), urinary bladder wall (4.9.10(-2) mGy/MBq) and thyroid (4.3.10(-2) mGy/MBq). The effective dose was estimated to be 2.2.10(-2) mSv/MBq. The results suggest that [(123)I]ADAM is of potential value as a tracer for single-photon emission tomography imaging of serotonin receptors in humans, with acceptable dosimetry and high brain uptake.     

Early Effects of Irradiation on [123I]-IMT and [18F]-FDG Uptake in Rat C6 Glioma Cells

BACKGROUND: Single-photon emission computed tomography (SPECT) using 3-[(123)I]-iodo-L-alpha-methyltyrosine ([(123)I]-IMT) and positron emission tomography (PET) using 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) are valuable tools for the distinction between viable tumor and radionecrosis in patients receiving radiotherapy for high-grade gliomas. However, to date, little is known about the early effects of radiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas. MATERIAL AND METHODS: To determine the early effects of irradiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas, in vitro studies were performed using rat C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common dose applied to patients receiving intraoperative radiotherapy. Subsequently, the early kinetics of [(123)I]-IMT and [(18)F]-FDG uptake in glioma cells were monitored for 3 days. RESULTS: Micromorphometric examinations of the irradiated glioma cells revealed that about 25% of the viable cells transformed into giant cells. [(123)I]-IMT uptake per 10(5) viable glioma cells was unchanged on the 1st day post irradiation, but showed a significant increase on the 2nd and 3rd day following radiotherapy (p < 0.01). In addition, there was a moderate increase in [(18)F]- FDG accumulation per 10(5) viable glioma cells during the first 3 days after irradiation (p < 0.05). The maximum increase in early [(123)I]-IMT uptake 1 h after application surpassed that of [(18)F]-FDG (p < 0.01). CONCLUSION: Rat C6 glioma cells show an early increase in [(123)I]-IMT and [(18)F]-FDG uptake following irradiation which may be partly due to giant cell formation. These data suggest that [(123)I]-IMT SPECT and [(18)F]-FDG PET may be promising procedures for the early prediction of the therapeutic response of gliomas to radiotherapy.