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Abstract: Using N-isopropyl-p-[123I]-iodoamphetamine(123I-IMP) and single-photon emission computed tomography (SPECT), the relationship between cerebrovascular reserve and the 123I-IMP redistribution phenomenon was investigated.The 50 patients who matched the inclusion criteria were divided into control and ischemia groups, and the redistribution phenomenon was examined on resting images. The delayed images showed higher 123I-IMP accumulation in lesions in the middle cerebral artery(MCA) area and anterior cerebral artery(ACA) area, these watershed areas in the ischemia group than in the control group, confirming that the redistribution phenomenon exists with statistical significance (Wilcoxon test; control group vs ischemic group in the ACA area[P = .002], ACA-MCA watershed area(P = .014), MCA area(P = .025), and MCA-posterior cerebral artery(PCA) watershed area(P = .002). The patients were then divided into 4 types according to the Kuroda grading system, and the difference in the redistribution phenomenon was investigated between type III and the other 3 types.Compared with type I and type II, type III had a significantly lower rate of decrease in the radioisotope (RI) count, verifying the redistribution phenomenon (Student t test: type I vs type III in the ACA area(P = .008), ACA-MCA watershed area(P = .009), MCA area(P < .001), and MCA-PCA watershed area(P = .002); type II vs type III in the ACA area(P = .004), ACA-MCA watershed area(P = .2575), MCA area(P < .001), and MCA-PCA watershed area(P < .001). No significant difference between type III and type IV was observed in any area [(Student t test: type III vs type IV in the ACA area(P = .07), ACA-MCA watershed area(P = .38), MCA area(P = .05), and MCA-PCA watershed area(P = .24)].The redistribution phenomenon is associated with resting cerebral blood flow (CBF), but not necessarily with cerebral vascular reactivity (CVR)., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

In this paper, data available on nuclear medicine imaging using commercially available radiopharmaceuticals for the differentiation, staging, and prediction or assessment of the response to treatment in tuberculosis (TB) are reviewed. Limited available studies suggest that single photon emission computed tomography (SPECT) using either 201Tl, 99mTc-sestamibi, or 99mTc-tetrofosmin is accurate (≥85%) and has a high negative predictive value (≥90%) for the differentiation of TB from carcinoma in patients presenting with a solitary pulmonary nodule (SPN). The criteria for detection of TB on 201Tl SPECT are nondepiction of the suspicious lesion in the delayed image or a negative retention index [washout on the delayed images (3–4 h postinjection) vs. the early image (5–15 min postinjection)] and a comparable-to-background uptake on 99mTc-sestamibi or 99mTc-tetrofosmin SPECT. Another SPECT tracer of potential interest for the differentiation of TB from malignant SPN that warrants further exploration, is N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). In contrast, 18F-fluorodeoxyglucose (18F-FDG) PET is unable to differentiate malignancy from TB and thus cannot be used as a tool to reduce futile biopsy/thoracotomy in these patients. A limited number of studies have reported on the potential of nuclear medicine imaging in assessment of the extent of disease in patients with extrapulmonary TB using 67Ga-citrate SPECT and 18F-FDG PET, respectively. 67Ga-citrate SPECT was shown to be as sensitive as bone scintigraphy for the detection of bone infection and was found to be complementary to computed tomography (CT) imaging. 18F-FDG PET was found to be significantly more efficient when compared with CT, respectively, in over half of patients for the identification of sites of lymph node involvement that were missed by CT and often the only sites of extrapulmonary TB identified. Unfortunately, 18F-FDG PET findings did not lead to alterations in treatment planning in any of the patients under study. Additional studies confirming these findings are urgently required. Similar to the setting of SPN, 18F-FDG PET cannot differentiate malignant lymph node involvement from lymph node involvement by TB. These results and the recent findings of Demura and colleagues using 18F-FDG PET further suggest that nuclear medicine imaging techniques could be used for the evaluation of therapeutic response. Prospective studies, focusing on specific subgroups of patients in whom such an imaging approach might be clinically relevant, for example in multidrug-resistant TB patients, are warranted. In acquired immunodeficiency syndrome patients, 67Ga scintigraphy proved to be a reliable and sensitive method for the primary detection and follow-up of opportunistic pneumonias, including TB. Combining 201Tl scintigraphy with 67Ga scintigraphy was shown to increase the specificity for both pulmonary and extrapulmonary TB, which is a 67Ga(+) and 201Tl(-) mismatch pattern in acquired immunodeficiency syndrome patients that is specific for mycobacterial infections. Finally, the results obtained using both SPECT and PET indicate that nuclear medicine could be an important noninvasive method for the determination of disease activity, detection of extrapulmonary TB, and determination of response to therapy.

General anesthesia is commonly used in experiments; however, its effects on cerebral circulation remain unknown. We measured cerebral blood flow using N-isopropyl[methyl 1,3-14C] p-iodoamphetamine (14C-IMP) and glucose utilization using 2-[1-14C] deoxy-D-glucose during general anesthesia with pentobarbital and chloral hydrate as well as conscious controls using rats and in-vivo autoradiography. Although a substantial reduction in 14C-IMP uptake was seen in the pentobarbital group, there was a significant increase in the chloral hydrate group. The ratio of cerebral blood flow against cerebral glucose utilization was 0.58 over all regions in the pentobarbital group, similar to the value for the controls, whereas this value was significantly high (over 1.5) in the chloral hydrate group. This decoupling effect should be considered when extrapolating experimental study data to normal physiology.

Background and Purpose: Although cerebral hyperperfusion after carotid endarterectomy (CEA) often impairs cognitive function, MRI does not always demonstrate structural brain damage associated with postoperative cognitive impairment. The purpose of the present study was to determine whether postoperative cortical neural loss, which can be detected by (123)I-iomazenil single-photon emission CT, is associated with cerebral hyperperfusion after CEA and whether it correlates with postoperative cognitive impairment., Methods: In 60 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>70%), cerebral blood flow was measured using N-isopropyl-p-[(123)I]-iodoamphetamine single-photon emission CT before and immediately after CEA and on the third postoperative day. The distribution of benzodiazepine receptor binding potential in the cerebral cortex was assessed using (123)I-iomazenil single-photon emission CT before and 1 month after surgery and was analyzed using 3-dimensional stereotactic surface projection. Neuropsychological testing was also performed preoperatively and at the first postoperative month., Results: Post-CEA hyperperfusion and postoperative cognitive impairment were observed in 9 patients (15%) and 8 patients (13%), respectively. Post-CEA hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 2.765 to 148.804; P=0.0031). Post-CEA hyperperfusion (95% CIs, 1.183 to 229.447; P=0.0370) and postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 1.003 to 77.381; P=0.0496) were also significantly associated with postoperative cognitive impairment., Conclusions: Cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment.

Objective: We examined the relationship between the perfusion reserve as measured by acetazolamide (ACZ)-challenge N-isopropyl-I-123-p-iodoamphetamine (IMP)-single-photon emission computed tomography (SPECT) and the degree of leukoaraiosis (LA) as estimated using magnetic resonance imaging., Methods: In 51 patients receiving IMP-SPECT with the resting state and ACZ challenge, the unaffected cerebral hemispheres were included in the present study. Mean cerebral blood flow (CBF) in the resting state and ACZ reactivity were acquired. Absolute CBF value and ACZ reactivity were compared among patients with LA grades 0, 1, and 2. The relationship between mean age and LA grade was also assessed., Results: No significant difference in the absolute CBF value in the resting state was observed among the 3 LA groups. Although vasoreactivity in LA grade 0 did not differ from that in grade 1, vasoreactivity in LA grade 2 was significantly lower (P < 0.05) than that in grades 0 or 1., Conclusions: The perfusion reserve is impaired in advanced LA.

Objective: To evaluate the efficacy of (123)I-IMP single photon emission computed tomography (SPECT) for the diagnosis of ocular malignant melanoma (MM)., Methods: Thirty-eight patients (18 males, 20 females) clinically suspected of having ocular MM were retrospectively examined in this study. The age of patients ranged from 8 to 81 years (mean 55.6 years). Twelve patients were finally diagnosed as having ocular MM. Orbital SPECT images were taken 15 min, 4 h, 24 h and 48 h after intravenous injection of 111-222 MBq (3-6 mCi) (123)I-IMP. (123)I-IMP uptake in the orbital tumor was visually evaluated as-(negative),+/-(equivocal), or+(positive). The uptake index (UI) and increase ratios (IRs) were calculated., Results: For visual evaluation, the accuracy of (123)I-IMP for the diagnosis of MM was 73.7% (15 min), 81.6% (4 h), 81.6% (24 h) and 86.8% (48 h). When UI and IR were calculated on both the MM and non-MM groups, the UI and IR of the MM group were significantly higher than those of the non-MM group (P<0.001). Moreover, the highest sensitivity (100%) and accuracy (94.7%) were obtained 48 h after (123)I-IMP administration when the cut-off value of UI was defined as 1.90., Conclusions: This study shows that (123)I-IMP SPECT is useful for the diagnosis of ocular MM. The UI values 48 h after the injection were efficient for the differentiation between MM and non-MM lesions.

Objectives: The aim of this study was to evaluate the usefulness of (123)I-iomazenil (IMZ) single photon emission computed tomography (SPECT) for the pre-surgical identification of epileptogenic areas in patients with temporal lobe epilepsy and to compare the results with those of (123)I-IMP SPECT and (18)Fluorodeoxyglucose positron emission tomography (FDG PET)., Methods: We examined seven patients with medically refractory temporal lobe epilepsy (five men and two women; mean age, 28 years) with no remarkable findings on magnetic resonance imaging. Before surgery, IMZ SPECT, IMP SPECT and FDG PET were all performed in the interictal state. Then, visual assessment and region-of-interest (ROI) analysis were performed on each image. Final definitions of the epileptogenic areas were made by electrocorticography and histopathology., Results: By IMZ SPECT, a decreased IMZ uptake in the ipsilateral temporal lobe was found in all patients, while a similar decrease in the contralateral temporal lobe was also found in one patient. In comparison to IMP SPECT, the extent of the abnormal area on IMZ SPECT was equal to that on IMP SPECT in one patient while it was more restricted to the epileptogenic area in five patients. In comparison to FDG PET, the extent of the abnormal area on IMZ SPECT was equal to that on FDG PET in three patients while it was more restricted in the epileptogenic area in four patients. In ROI analysis, decreases of IMZ, IMP and FDG uptake were observed in the epileptogenic area, although they were not statistically significant., Conclusions: IMZ SPECT was considered to be useful for pre-surgical determination of the epileptogenic areas in temporal lobe epilepsy with no remarkable MRI findings, and it was also found to be superior to IMP SPECT and FDG PET for this purpose.

Background and Purpose: Crossed cerebellar diaschisis (CCD) refers to reduced metabolism and blood flow in the cerebellar hemisphere contralateral to a cerebral lesion. Many cortical areas have been reported to cause CCD without consideration of confounding factors. We performed single-photon emission computed tomography (SPECT) in patients with cortical infarction to identify regions independently related to CCD, controlling for possible confounding effects., Methods: Patients with unilateral cortical infarction (n=113; 75 male, 38 female; mean+/-SD age, 66+/-13 years) underwent SPECT of the brain with N-isopropyl-p-[(123)I]iodoamphetamine ((123)I-IMP). Regional cerebral blood flow was measured autoradiographically. Asymmetry indices (AIs) were calculated on the basis of ratios representing symmetrical regional cerebral blood flow in the cerebellum and 16 cerebral regions. CCD was defined as AI for cerebellum >0.1. AIs for 16 cortical regions were considered for both dichotomous and continuous variables for analysis of CCD occurrence by means of backward logistic regression., Results: For dichotomized variables, hypoperfusion of postcentral (odds ratio [OR]=7.607; 95% CI, 2.299 to 25.174) and supramarginal (OR=3.916; 95% CI, 1.394 to 11.003) regions independently influenced CCD. For continuous variables, hypoperfusion of postcentral (OR=1.044; 95% CI, 1.019 to 1.068) and supramarginal (OR=1.021; 95% CI, 1.001 to 1.041) regions (and, as a negative factor, medial occipital regions; OR=0.942; 95% CI, 0.895 to 0.991) independently influenced CCD., Conclusions: Many cortical areas apparently do not contribute to CCD. Correspondence of CCD between dichotomized and continuous analyses suggests that location of a lesion, not severity, is the main determinant of CCD.

Background and Purpose: Patients with carotid occlusive disease and stage 2 cerebral hemodynamic failure, characterized by an increased oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) and otherwise known as misery perfusion, have a high risk of cerebral ischemia and subsequent stroke. In clinical practice, the detection of patients with misery perfusion through the use of widely available, noninvasive, and cost-effective modalities such as single-photon emission computed tomography (SPECT) is extremely important., Methods: We evaluated the relationships between the regional hemodynamic status of cerebral circulation, measured with split-dose [123I] N-isopropyl-p-iodoamphetamine SPECT (123I-IMP SPECT) and an acetazolamide challenge, and hemodynamic parameters, including OEF measured with PET, in 27 patients with both unilateral and bilateral carotid occlusive diseases., Results: A significant negative correlation was found between the SPECT-measured cerebrovascular reserve after acetazolamide administration and both the PET-measured OEF and cerebral blood volume. Neither the cerebrovascular reserve nor the cerebral blood flow index, when expressed as a SPECT-measured cerebrum-to-cerebellum ratio, was useful for detecting lesions with an elevated OEF. However, a combination of the cerebrovascular reserve and cerebral blood flow index showed high sensitivity, specificity, and positive predictive value for the detection of misery perfusion., Conclusions: Our study suggests that split-dose 123I-IMP SPECT with an acetazolamide challenge could be useful for screening patients with misery perfusion in carotid occlusive diseases.

The Mini-Mental State examination (MMSE) is frequently used to assess the cognitive function of neurological patients. The purpose of this study was to investigate associations between regional cerebral blood flow (rCBF) and MMSE scores in Alzheimer's disease (AD) and localization of cognitive functions. Fifty-nine patients with probable AD (21 males and 38 females; mean age 74 years) and 12 normal volunteers (five males and seven females; mean age 73 years) were studied. CBF was measured by SPECT using the N-isopropyl-p-[(123)I]iodoamphetamine autoradiography method. The CBF images were reconstructed in parallel with the orbitomeatal line and parallel to the long axis of the temporal cortex. Regions of interest were set in the cerebral and cerebellar cortex. Multivariate analysis was performed by the step-wise method, using each section of the MMSE as the dependent variable and the rCBF ratio as the independent variable. The decline in rCBF in the parietal cortex and hippocampus reflected disorientation, and the most significant cortex affecting scores on each section of the MMSE were found to be the anterior temporal cortex for registration, the frontal cortex for attention and calculation, the medial temporal cortex for recall, and the posterior temporal cortex for language.

We report on six patients with chronic pulmonary embolism who underwent 123I-IMP and 99Tcm-MAA lung SPET before and after thromboendarterectomy. 123I-IMP lung SPET can assess the viability of lung parenchyma, because it is a non-particulate agent that accumulates in the endothelial membranes of pulmonary capillaries. Chronic pulmonary thromboembolism accompanied by pulmonary hypertension has a poor prognosis that may be improved only by thromboendarterectomy. We compared 123I-IMP and 99Tcm-MAA lung SPET in terms of functional improvement after such surgery. After thromboendarterectomy, all six patients were functionally improved, according to the criteria of the New York Heart Association. The pre- and post-surgery percentage of vascular obstruction did not differ significantly with 99Tcm-MAA lung SPET (44.8 +/- 11.2% and 32.5 +/- 15.6% pre- and post-surgery, respectively). In contrast, 123I-IMP lung SPET revealed a significant pre- versus post-surgery difference (15.5 +/- 9.5% and 3.3 +/- 5.9% pre- and post-surgery, respectively). 123I-IMP lung SPET could be useful for evaluating thromboendarterectomy because pulmonary parenchymal viability owing to arterial microvasculature can be estimated.

Bulimia nervosa is an eating disorder of which characterized psychopathological symptoms are a recurrent episode of binge eating. The changes in cerebral blood flow (CBF) in a patient with bulimia nervosa between his or her different eating phases are presented. CBF was measured quantitatively by means of single photon emission computed tomography using I-123 N-isopropyl-p-iodoamphetamine. CBF of the global brain during a binge-eating phase was higher than that during an anorexic state phase. In the anorexic state, the CBF in the temporal, parietal, and occipital lobes on the right side was lower than that on the left side. In the binge-eating state, a lack of laterality between the right and left cerebral hemispheres was found. This finding suggests that cerebral activity differs between the two phases, and that asymmetry is dependent of the eating state.

N-isopropyl-p-I-123-iodoamphetamine (123I-IMP) is extracted by the brain in proportion to regional blood flow. It is particularly useful in the clinical assessment of various pathological conditions related to altered cerebral flow. Moreover, it has been reported that 123I-IMP is avidly incorporated into melanin and melanotic melanoma. We evaluated 123I-IMP scintigraphy using either planar or single photon emission tomography (SPET) studies in 10 patients with malignant melanoma. The patients were classified into two groups according to the tumour site: Group A, six patients with primary or metastatic cutaneous malignant melanoma of the extremity with planar scintigraphy; Group B, four patients with primary malignant melanoma of other organs with planar scintigraphy and SPET. In Group A, tumour uptake was demonstrated in four of six patients; in Group B, three of four patients had tumour accumulation on SPET and planar scintigraphy. SPET revealed the exact tumour localization, even in the case of a tumour located in the lung. These results suggest that planar scintigraphy using 123I-IMP is useful in the detection of malignant melanoma. Furthermore, more clear tumour localization is possible with SPET, even in the case of a tumour located in the lung.

The microsphere model and the continuous withdrawal of arterial blood have commonly been used in clinical studies when measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission tomography. The method is considered to underestimate rCBF because of the washout of tracer from brain tissue; however, the extent of this underestimation is not known. To assess whether this underestimation can be determined quantitatively, we performed simulation analysis based on the microsphere model and the two-compartment model [influx, K1(rCBF); and outflux, k2(washout)] using the time-activity curves of 123I-IMP in arterial blood [Ca(t)] of 10 subjects. With the microsphere method, rCBF values fell as time post-injection increased. The extent of underestimation of rCBF was 4.7 +/- 0.28% (mean +/- S.D.) at 5 min, 10.2 +/- 0.42% at 10 min and 15.2 +/- 0.55% at 15 min. There was little variation in the extent of underestimation and it was not dependent on the Ca(t) of the subjects. We therefore considered the results to be generally applicable to various studies of the microsphere model. As 4.7% is considered to be negligible in clinical studies, we conclude that the microsphere model can be applied to obtain accurate measurement of rCBF up to 5 min regardless of washout.

Twenty patients with 58 extrahepatic metastases of hepatocellular carcinoma (HCC) (41 bone, 5 lung, 6 peritoneum, 4 adrenal glands, 1 brain, 1 lymph node) underwent 123I-iodoamphetamine (123I-IMP) and gallium-67 (67Ga) scintigraphy. The rate of positivity with 123I-IMP planar imaging was 44% above the level of the diaphragm and 76% below the diaphragm, with an overall sensitivity of 62%. The combination of 123I-IMP scintigraphy and single photon emission tomography enabled positive visualization of an additional six metastatic foci: three in the adrenal glands, one in the peritoneum, one in the cranium and one in a rib. The rate of positivity with 67Ga planar imaging was 75% above the level of the diaphragm and 45% below the diaphragm, with an overall sensitivity of 58%. Our findings suggest that 123I-IMP is effective for detecting extrahepatic metastases of HCC, particularly those below the diaphragm.

The aims of this study were (1) to compare N-isopropyl-p-[I-123]-iodoamphetamine (123I-IMP) SPET with computed tomography (CT) in chronic-stage head trauma patients with neurological abnormalities and (2) to quantify regional cerebral blood flow (rCBF) in patients with chronic-stage head trauma. 123I-IMP SPET and CT were performed in 23 patients with chronic-stage head trauma and 12 normal controls. Both types of imaging were evaluated visually. In addition for the SPET images, the rCBF in 12 regions (bilateral frontal cortex, temporal cortex, parietal cortex, occipital cortex, perilolandic area, cerebellum: total 276 regions) was analysed quantitatively using a reference sampling method. In total, 39 focal lesions related to neurological abnormalities were detected. Although 22 (56.4%) lesions were observed using both CT and SPET, another 17 (43.6%) were detected by SPET only. The mean rCBF in the localized lesions of each lobe, which correspond to low-density areas (LDAs), were lower on CT than those of each lobe seen only on SPET. These rCBF values were lower than the mean rCBF values in the lobes of the controls. The mean rCBF values in each lobe with visually normal tracer uptakes were also significantly lower in the 23 patients than in the controls. 123I-IMP SPET is useful for demonstrating brain dysfunction in morphologically intact brain regions and for providing objective evidence to account for the clinical presentation of patients presenting with chronic traumatic brain injury.

We developed a new method for quantitative measurement of regional cerebral blood flow (rCBF) using one-point arterial sampling with N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) and single photon emission computed tomography (SPECT) based on the microsphere model. Although the conventional microsphere method requires both the continuous withdrawal of arterial blood (integral of Ca(t)) and treatment of the blood with octanol to obtain the fraction of true tracer activity in the integral of Ca(t) (N), the new method does not require these two procedures. We examined 14 patients to analyse the correlation between the integral of Ca(t)N and a small arterial sample obtained at one time point [one-point Ca(t)] after the injection of 123I-IMP without octanol treatment. The integral of Ca(t)N was calculated from one point Ca(t) using the regression line of the correlation. An error of 8.1% in the calculated value compared to the actual value of the integral of Ca(t)N, could be inferred from one-point Ca(t) obtained at 6 min after the injection. Then regional cerebral blood flow was measured by the method and a significant correlation was obtained with rCBF measured using the 133Xe inhalation method (r = 0.773). The one-point Ca(t) method provides fast, easy, accurate and non-invasive measurement of rCBF without inserting catheters and without treatment of arterial blood with octanol.

Regional cerebral blood flow (rCBF) was measured using N-isopropyl-123I-iodoamphetamine (123I-IMP) with single photon emission computed tomography (SPECT) in 27 patients with diabetes mellitus with an average age of 64.1 years and with an average fasting plasma glucose of 145 mg dl-1. Their data were compared with those of 12 non-diabetic subjects with an average age of 64.6 years. None had cerebral infarction on computed tomographic (CT) studies. There were no significant differences in the physiological or laboratory data between the diabetic and non-diabetic groups except for their fasting plasma glucose and HbA1c levels. A reference sampling method using continuous arterial blood sampling was employed to quantify the rCBF. The average rCBF in each region of the cerebrum and cerebellum was significantly lower in the diabetic group than in the non-diabetic group (P < 0.01). Although a definite cause was obscure, the rCBF of the diabetic patients was reduced even in the absence of findings indicative of cerebral infarction on a CT study.

In fifteen cases of arteriovenous malformation (AVM), serial examinations of regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) and N-isopropyl-(123I)p-iodoamphetamine were performed. On SPECT images, the nidus was visualized as a focal rCBF defect in all cases preoperatively and seven of these cases had abnormal decreased perfusion areas in the tissues adjacent to the nidus. In five cases, the postoperative SPECT images on the day after surgery revealed an abnormal increased perfusion area adjacent to the nidus and in one case the increased perfusion was accompanied by a massive intracerebral haemorrhage detected by brain computed tomography (CT). In seven cases, postoperative SPECT images showed widespread abnormal decreased perfusion areas in the surrounding tissues and brain CT revealed either intracerebral haemorrhage or significant cerebral oedema. In the other three cases, no remarkable rCBF changes were found in comparison with the pre-operative study. There was a tendency for the preoperative abnormal decreased perfusion area adjacent to the nidus to correlate with the postoperative hyperperfusion and for the postoperative abnormal decreased perfusion area to reflect brain damage.

Background and Purpose: The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients., Methods: Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions., Results: Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area., Conclusions: The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction.

A dual isotope, single photon emission tomography (SPECT) technique using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 123I-iodoamphetamine (IMP) was investigated to determine its suitability for assessing regional cerebral blood flow (rCBF) changes resulting from cognitive activation. The similarity of the 123I-IMP and 99Tcm-HMPAO distributions under the same physiological conditions was first investigated by administering the two agents to human subjects (n = 8) either simultaneously or at different times but during the performance of the same task. Normalized ratio images generated from the 99Tcm and 123I data showed that the two tracers distributed similarly in the left and right cerebral hemispheres when administered under similar physiological conditions. There was, however, a significant anterior/posterior gradient that appears to be the result of partial volume effects due to small differences in spatial resolution of the two agents. In two subjects, 99Tcm-HMPAO was administered during a resting period with eyes-closed and 123I-IMP was injected later during visual checkerboard stimulation. Ratio images showed a localized increase in the occipital lobes during the visual stimulation consistent with the expected increase in rCBF. The dual isotope strategy appears promising for study of changes in rCBF due to cognitive activation.

Schizophrenia is a major psychiatric problem common in the younger population. Structural imaging and findings on autopsy have not yet revealed a specific deficit in these patients. Uncertainty in clinical diagnosis based on a set of signs and symptoms is another drawback in the management of this patient population. Regional cerebral blood flow studies (rCBF) using single photon emission computed tomography (SPECT) offers the opportunity to study the underlying phenomenon and to detect the specific functional deficits in schizophrenia.

Single photon emission computed tomography (SPECT) using N-isopropyl-p-(123I)iodoamphetamine (123I-IMP) and 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was performed in 25 patients with different clinical stages of AIDS encephalopathy. The average interval between the two examinations was 7 days. In 15 of the 25 cases (60%) 99Tcm-HMPAO scans were different from 123I-IMP scans. Uptake defects of different extent were observed in 8 of 25 cases (32%), of different extent and different location in 3 of 25 cases (12%) and of identical extent but of different location in 4 of 25 cases (16%). Differences in the uptake patterns of 123I-IMP and 99Tcm-HMPAO with regard to extent and/or location were more commonly shown in patients with early acquired immunodeficiency syndrome (AIDS) encephalopathy (P = 0.0372). In this group, 99Tcm-HMPAO showed uptake defects of greater extent more frequently than did 123I-IMP (P = 0.0156). Our data indicate different brain uptake mechanisms of 123I-IMP and 99Tcm-HMPAO in early and advanced AIDS encephalopathy.

Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach.

Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

Background and Purpose: The purpose of this study was to determine utility of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution in predicting neurological and language outcome., Methods: We prospectively studied 29 patients with unilateral hemispheric ischemic cerebral infarction using the neuroimaging method of single-photon emission computed tomography and the above tracer. Four different imaging measures reflecting late tracer distribution or redistribution and three measures indicative of the patients' overall neurological or language outcome at 3 months were used in the data analysis. All patients had neuroimaging within 30 days of infarction, and 14 patients were imaged within 10 days of infarction. Data analysis was performed for all patients combined and then separately on the groups imaged within 10 days of and more than 10 days after infarction., Results: The volume of the late image defect significantly correlated with one measure of neurological outcome in the whole group and in those imaged more than 10 days after cerebral infarction. However, these results are difficult to explain based on the present understanding of the physiology of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution., Conclusions: We feel that the pattern of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution is probably not useful as an independent predictor of neurological and language outcome.

Regional cerebral perfusion was studied in three patients with the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, using single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP). Accumulation of the tracer was relatively decreased in the parietooccipital regions and also in the frontotemporal regions after stroke-like episodes. However, quantitative regional cerebral blood flow (rCBF) measurement showed that rCBF was relatively well preserved even at these sites, and a hyperemic state was observed at the sites of normal accumulation. IMP SPECT may be useful in the diagnosis and assessment of the progress of the MELAS syndrome.

Cerebral SPECT studies with N-isopropyl-iodo-amphetamine (123I) (IMP) were performed in patients who had suffered cranio-facial trauma, with and without loss of consciousness (LOC). The results were compared with computed tomography (CT). Nine out of ten of those with LOC had normal CT scans and evident photopaenia in IMP studies. It is clear that IMP SPECT scans complement CT in the investigation of patients who have suffered cranio-facial trauma.

N-isopropyl-p-[125I]iodoamphetamine (125I-IMP) binding to crude synaptosomal membranes of rat brain was saturable and pharmacologically displacable. Scatchard analysis of binding data revealed an apparent dissociation constant, KD of 56.2 +/- 5.2 microM, and the estimated maximum number of binding sites, Bmax of 7.5 +/- 1.1 nmoles mg-1 protein; and competition studies demonstrated structure activity relationships among structural analogues of arylalkylamines. These findings suggest that the retention mechanism of IMP in the brain is probably associated with saturable binding of IMP to extreme high-density, relatively low-affinity binding sites rather than any of the well-known amine receptors.

Both I-123 IMP scintigraphy and MRI have been suggested as sensitive detectors of changes shortly after acute cerebral infarction. We compared the uptake of N-isopropyl I-123 p-iodoamphetamine (IMP) and MR spectroscopy of the brain after internal carotid artery ligation. Thirteen gerbils were lightly anesthetized with ether. After neck dissection, an internal carotid artery was occluded. After 2.8 hours, 100 muCi I-123 IMP was injected intravenously into the 13 experimental animals plus three controls. Seven gerbils remained asymptomatic while six developed hemiparesis. At 3 hours after ligation, the animals were killed. The brains were bisected and T1 and T2 relaxation times were determined for the right and left hemispheres by MR spectroscopy immediately after dissection. I-123 IMP uptake was then determined in the samples. Interhemispheric differences in uptake for I-123 IMP were 0.1 +/- 1.7% (SEM) in the control, 33.5 +/- 10% in the asymptomatic and 54.6 +/- 9.7% in the symptomatic animals. Significant differences were seen with I-123 IMP in 6/7 asymptomatic and 6/6 symptomatic animals. In conclusion, I-123 is more sensitive than T1 or T2 relaxation times for the detection of cerebral perfusion abnormalities. Prolongation in T1 and T2 relaxation times correlates closely with increased brain tissue water content and the development of symptoms, indicators of structural brain damage and probable infarction.

In this study we assessed regional cerebral blood flow in patients with signs and symptoms of acute stroke using single-photon emission computed tomography (SPECT) and N-isopropyl I-123 p-iodoamphetamine (IMP). Twenty-five patients with acute cerebral infarction had both IMP brain perfusion studies and CT scans performed within one week of each other; 22 had positive and three had negative perfusion studies. Of the 22 patients who had positive perfusion studies, six had negative CT studies initially. In the 16 patients who had abnormal CT studies, eight of the studies depicted areas of edema that were smaller than the perfusion deficits noted on the IMP studies and eight had areas of edema that were approximately equal in size to the perfusion defect. Of the three patients with normal IMP studies, two had normal CT studies and one had a positive CT study showing a 3-mm lacunar infarction. Using eight control patients, mean count rates per tissue volume normalized for the injected dose was calculated. Similarly, the quantitative data from regions of interest in the stroke patients were calculated and compared to the control patients or to a normal region in the uninvolved hemisphere in the same patients. SPECT with IMP was used to assess regional brain perfusion in acute cerebral infarction. Perfusion abnormalities were seen in our patients when the CT scan was normal, and quantitative data could be used to approximate regional cerebral blood flow in these patients when compared to the normal patient population.

Local cerebral blood flow (LCBF) images of HMPAO and IMP were directly compared in experimental brain ischaemia in the same rats using a double-tracer autoradiographic technique. Both images were identical in distribution throughout the whole flow areas. However, LCBF values were much lower in HMPAO than in IMP. The results suggest that HMPAO acts as a chemical microembolus in rat brain in both low and high flow areas; however, a quantitative flow measurement is difficult in an HMPAO study.

The first clinical data is given on 99Tcm-hexamethylpropyleneamine oxime (HM-PAO) in normal subjects and patients with established stroke. Regional cerebral blood flow maps (rCBF) have been recorded and displayed in tomographic mode with this new radiopharmaceutical. Good images were obtained, comparable to those achieved with 123I-isopropylamphetamine (IMP).

Amines like N-isopropyl-p-123I-iodoamphetamine (IMP) and hydroxy 123I-iodobenzyl propyl diamine (HIPDM) associated with brain tomoscintigraphy have proved their worth for detecting ischaemic abnormalities. Even though the chemistry of their metabolism and their biodistribution are not fully understood, their application in the study of parenchymal impairment in stroke and reversible ischaemia yields additional information compared to the other methods of imaging like CT or MRI. The concept of a steady state in brain with a wash in/wash out model has been considered especially with IMP, to explain the evolution of the activity pattern with time when comparing early and delayed images. (This review leads to foresee the prognosis of of ischaemic diseases when redistribution is taken into account.)

p-(123I and 131I)iodo alpha,alpha-dimethylphenethylamine (p-iodophentermine, IP) as the alpha-methylated analogue of iodoamphetamine has been prepared. It is hoped that this methyl substitution will increase the lipophilicity of the agent, enhance resistance to metabolism by monoamine oxidase, and will result in increased initial uptake and slower washout from the brain as compared to N-isopropyl-p-(123I)iodoamphetamine. IP was prepared by diazotization of p-aminophentermine followed by decomposition of the diazonium salt with KI. Radioiodinated IP was prepared either by the solid-phase isotopic exchange reaction or by decomposition of the piperidinotriazene derivative with a radiochemical yield of 40-60%. Biodistribution of 131I-IP in rats showed brain uptake in the range of 1.7% dose g-1 at 5, 30 and 60 min. Imaging studies with 123I-IP in dogs showed high brain extraction and slow washout of activity.

Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMP in two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8-1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was considerable extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.

Twenty patients with stroke were studied for cerebral blood perfusion abnormalities using N-isopropyl I-123 p-iodoamphetamine (IMP) and rotating dual gamma camera emission computed tomography (ECT). After a single scan, multiple transverse, coronal and sagittal section images were reconstructed with a minicomputer. In eighteen patients, we determined the values of regional cerebral blood flow (rCBF) in the region of interest using an image. Transmission computed tomography (CT) studies were also performed on the same day. ECT showed cerebral perfusion abnormalities in all cases, while CT showed abnormalities in only 10 cases. This technique seems to be useful for evaluating the rCBF in the deep brain.

Seventeen chronic cerebral infarcts were investigated by a highly sensitive, dedicated brain single photon emission computerized tomography system using 123I-isopropyl iodoamphetamine (IMP) and 133Xe. IMP uptake was measured 10 minutes, 2 hours, and 5 hours after injection, and regional cerebral blood flow was measured with 133Xe. In 4 cases a positron emission tomography system was used to measure the rCBF and the regional metabolic rate of oxygen with C15O2 and 15O2. The results obtained allowed us to identify 2 abnormal zones. One, the "central area," was characterized by a severe decrease in IMP uptake and rCBF averaging 34% and 46% respectively and by a hypodense image on the x-ray computerized tomography scan. The second, the periinfarct or "peripheral area" was characterized by a moderate decrease in IMP uptake and regional cerebral blood flow averaging 13 and 19% respectively; this area extended around the central area and had a normal density on computerized tomography scan. The IMP hypofixation of the peripheral area observed at the 10th minute tended to disappear at the 5th hour. The volume of this area was often found to be quite large, covering more than 30% of a hemisphere whereas the central area did not exceed 25%. Volume appeared to be correlated with the neurological status of the patient. The nature of the peripheral area is not established with certainty. It may be caused by deafferentation of areas not directly affected by the ischemic insult and/or selective ischemic neuronal loss. The results stress the important role played by the peripheral area, which may be useful in establishing the prognosis and evaluating the efficacy of therapy in individual stroke cases.

The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92% to 100%) than computerized tomography (55% to 86%) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69%. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50% to 100%, while specificity has ranged from 97% to 100%. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.

The results of previous reports on the usefulness of brain perfusion single photon emission computed tomography (SPECT) in predicting the outcome of patients with acute cerebral infarction are conflicting. We therefore studied brain perfusion in 64 patients with a single supratentorial infarction. Contradictory to previous results the perfusion defect volume estimated from transversal and coronal slices correlated significantly with both presenting clinical findings and outcome. Although the clinical status at admission also correlated well with outcome, there was a subgroup of patients in which the favourable outcome was predicted only by SPECT and not by physical or any other examination at admission.

Regional cerebellar blood flow was measured in a patient with left-sided ataxic hemiparesis, using single-photon emission computed tomography and N-isopropyl-p-[123I]Iodoamphetamine. X-ray computed tomography revealed a small infarct in the paramedian portion of the right upper basis pontis. Blood flow was markedly reduced in the contralateral cerebellar hemisphere corresponding to the side of ataxia. The present study emphasizes the value of the three-dimensional functional imaging of the cerebellum to investigate the responsible lesion for ataxia and to study function of the cerebro-cerebellar circuits.

Early and late brain distribution of iodine-labelled N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM) and iodine labelled N-isopropyl-p-iodoamphetamine (IMP) were compared in rat and one human patient with a recent stroke in the right middle cerebral artery area. In rat, an important 'redistribution' of cerebral activity was observed in various areas of the brain, mainly white matter, whereas no such observation was made with HIPDM. In the patient, the right area was hypoactive during the early SPECT with IMP and HIPDM, and redistribution was observed in the late SPECT only with IMP. We suggest that while HIPDM appears to reflect regional cerebral perfusion, IMP distribution is dependent upon metabolic brain activity.

Lung endothelial binding sites of N-isopropyl-123I-p-iodoamphetamine (123I-IMP) were assessed employing the principle of competitive binding assay adapted for in vivo measurement using a computer-scintillation camera technique. A noninvasive modification of the Chinard-Crone technique was applied to the study of pulmonary extraction. 123I-IMP, the test cellular tracer and 99Tcm-dextran the vascular reference tracer were used in dogs to determine the first pass pulmonary extraction of 123I-IMP. The lung extraction of 123I-IMP decreases progressively from 90 to 62% as the amount of propranolol (administered 10 min prior to the injection of 99Tcm-dextran) gradually increased from 0 to 20 mg. The dissociation constant of 123I-IMP lung binding sites reaction in the presence of propranolol was calculated by Scatchard plot and found to be 10 mg. The in vivo procedure described in this paper will enable us to develop a model for the assay of the binding sites in the lungs for amine and its influence in both health and disease.