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Unlabelled: A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion., Methods: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET., Results: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method., Conclusion: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.

Iodine-123-labeled N-isopropyl-p-iodoamphetamine (IMP) has been reported to be an excellent tracer for mapping cerebral blood flow with single-photon emission computed tomography (SPECT). Clinical interpretation of these SPECT images, however, requires further understanding of the kinetics of IMP in the human brain. In order to evaluate the kinetic behavior of IMP in normal and diseased areas, we measured flow and back-diffusion rates with serial dynamic SPECT scans following an intravenous bolus injection of IMP using a multi-detector SPECT scanner. Arterial input function was determined by octanol extracted radioactivity of serial arterial blood samples. Average values for influx rate (K1) and back-diffusion rate (k2) were 0.43 ml/g/min and 0.014 min-1 in the normal cerebral cortex, 0.43 and 0.013 in the basal ganglia, 0.28 and 0.012 in the white matter and 0.48 and 0.016 in the cerebellar hemisphere. The partition coefficient (K1/k2 ratio) was 32.4 ml/g in the cerebral cortex, 35.3 in the basal ganglia, 24.7 in the white matter and 30.4 in the cerebellum. The K1-to-k2 ratio in the infarcted and ischemic regions as well as in the tumor was smaller than that of the normal cortex. Accurate measurement of local cerebral blood flow (LCBF) based on the microsphere model was possible only on the early SPECT images, but a relative pattern of LCBF can be assessed with SPECT images obtained within 1 hr after injection except for tumors.

The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a "physical" phenomenon (only flow related) rather than a "biologic" one.

Radionuclide imaging with N-isopropyl-(I-123)p-iodoamphetamine ([123I]IMP) was performed in a patient with recurrent bronchial carcinoid tumor. Increased accumulation of [123I]IMP was observed in the known lesions of the brain and neck on both tomographic and planar images. Scintigraphy also revealed unknown metastatic lesions of the paraaortic lymph nodes, which were later confirmed on x-ray CT. Iodine-123-IMP may have a potential role in evaluating carcinoid tumors.

Regional cerebral dynamics of N-isopropyl-(123I)p-iodoamphetamine (IMP) in the human brain were studied using a multi-detector single photon emission computed tomography (SPECT) scanner in 35 subjects both normal and with a variety of neurological conditions. Distribution of IMP in the brain was also compared with regional cerebral blood flow (CBF) measured by positron emission tomography (PET) in 15 of these 35 cases. A significant regional difference in temporal changes of radioactivity was observed among normal brain structures. A rapid increase with early washout of the tracer was shown in the cerebellum and the occipital cortex, while the basal ganglia revealed a relatively slow increase and prolonged retention, indicating the regional difference in extraction and/or retention of IMP among the cerebral tissues. In cases with unilateral hypoperfusion, the percentage of the activity in the lesion to that in the contralateral normal cortex on the early SPECT was correlated well with that on CBF measured by PET (r = 0.870, p less than 0.001). However, the contrast on the SPECT image decreased with time after injection; 84.0 +/- 7.4% on the SPECT at 5-20 min scan, 87.6 +/- 7.6% at 35-50 min scan and 96.2 +/- 6.3% at 5 hr scan. In a case with a brain tumor having high blood flow documented by PET, increased accumulation of IMP was observed in the tumor on the early images obtained within 20 min followed by a rapid washout. These findings suggested altered extraction and/or retention of IMP in normal and diseased tissues, and these factors should be considered for the assessment of distribution and redistribution of IMP.

Application of chemical methods for characterizing the in vivo behavior of iofetamine HCI 123I (IMP) has shed light on the metabolism of iofetamine in animals and humans. A successful technique consists of ethyl acetate extraction of the metabolites from tissue samples acidified with perchloric acid, separation of the mixture by high performance liquid chromatography, and quantitation of the radioactive components with a sensitive scintillation detector. Metabolism of iofetamine HCI 123I proceeds sequentially from the N-isopropyl group on the amphetamine side chain. The first step, dealkylation to the primary amine p-iodoamphetamine (PIA), occurs readily in the brain, lungs, and liver; activity in the brain and lungs consists of only IMP and PIA even 24 hr after administration. The rate-limiting step appears to be deamination to give the transitory intermediate p-iodophenylacetone, which is rapidly degraded to p-iodobenzoic acid and conjugated with glycine in the liver to give the end product of metabolism, p-iodohippuric acid, which is excreted through the kidneys in the urine.

Iodoamphetamine (IMP) was shown by in vitro assay to have a high uptake by human melanotic melanoma cells, as compared to amelanotic melanoma cells. Eleven patients with proven malignant melanoma (MM) and 3 normal subjects were imaged at 2-4 hr and 16-24 hr after the i.v. injection 5 mCi (185 MBq) of [123I]IMP. One patient had a recurrent tumor that was subsequently shown to be squamous cell carcinoma. The index lesion was not visualized in the three patients with amelanotic melanomas. The index lesion/lesions were visualized in six of the seven other patients, except for 4/16 nodules in one patient. The seventh patient had a large, necrotic melanotic tumor that was not visualized, but an unsuspected lesion in the iliac nodes was detected. Multiple unsuspected lesions were detected in a second patient. While many lesions were seen at 2-4 hr, all lesions (other than a patient with small bowel disease) were seen best at 16-24 hr. No eye uptake was observed in any patient or control subject. Testicular uptake was seen in all males at 16-24 hr. Iodine-123 IMP appears to be a useful agent for the detection and follow-up of patients with melanotic MM.

Temporal changes in brain uptake of 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) were studied by means of a multi-detector single photon emission computed tomography (SPECT) scanner. Serial dynamic SPECT scan was performed for 50 min following an i.v. bolus injection of IMP in 30 patients with various neurologic diseases. In 18 of them the radioactivity in the lung was also recorded by a single probe detector during the serial dynamic SPECT scan. Brain activity showed a gradual increase after the injection of IMP, reaching 63 +/- 7% of the maximum activity at 5 min and 90 +/- 5% at 20 min. The lung clearance showed a large variation among the individual cases; 29 to 72% (52 +/- 11%) of the initial peak activity at 20 min and 22 to 57% (41 +/- 9%) at 50 min after the injection. A significant positive correlation was observed between the clearance half-time in the lung and the time to reach 90% of the maximum activity in the brain (r = 0.86, p less than 0.001). These results suggested that brain uptake of IMP is influenced by the lung clearance and the optimum time to start SPECT data acquisition using a conventional rotating gamma camera system is 20 min after the injection.