Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.     

Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with <Superscript>99m</Superscript>Tc-ECD SPECT

Introduction Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information. Methods Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer (^99mTc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI. Results The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (−46.52%), negative rCBV increment (−13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student’s t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection. Conclusions Perfusion MRI before and after acetazolamide administration compares favourably with ^99mTc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study. The first and second author contributed equally to this study.     

Evaluation of brain tumor recurrence by <Superscript>99m</Superscript>Tc-tetrofosmin SPECT: a prospective pilot study

Objective The differentiation between brain tumor recurrence and post-irradiation injury remains an imaging challenge. Computed tomography (CT) and magnetic resonance imaging (MRI) cannot always distinguish between the two. Although glioma cell line studies substantiated a plausible imaging superiority of ^99mTc-tetrofosmin (^99mTc-TF) over other radiopharmaceuticals, little has been reported on its in vivo imaging properties. We assessed ^99mTc-TF single-photon emission CT (SPECT) in cases where morphologic brain imaging was inconclusive between recurrence and radionecrosis. Methods A total of 11 patients (7 men, 4 women) were evaluated. The initial diagnosis was glioblastoma multiforme (4), anaplastic astrocytoma (1), anaplastic oligodendroglioma (3), grade-II astrocytoma (2), and low-grade oligodendroglioma (1). All patients had been operated on and then received adjuvant external-beam radiotherapy. After a mean follow-up period of 25 months, there was clinical suspicion of recurrence, for which ^99mTc-TF SPECT was performed. Results In 8/11 cases, an abnormally increased tracer uptake appeared in the region that CT and/or MRI indicated as suspicious; in half of these cases, recurrence was confirmed histologically after surgery and in the other four by growth of the lesion over a 6-month follow-up period, and clinical deterioration. The remaining 3/11 patients had faint tracer uptake in the suspicious region, compatible with radiation injury; these lesions remained morphologically unaltered in a mean 12-month follow-up period, with no clinical deterioration in the patient's condition, a course strongly favoring the diagnosis of radiation injury. Conclusions Metabolic brain imaging by ^99mTc-TF could offer useful information in the workup of treated brain tumors, where radiomorphologic findings between recurrence and radionecrosis are inconclusive.     

Pre-operative localisation of hyperfunctional parathyroid tissue with <Superscript>11</Superscript>C-methionine PET

Purpose Previous studies have shown high sensitivity of positron emission tomography (PET) with ¹¹C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of ¹¹C-methionine PET and ^99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of ¹¹C-methionine in those patients with inconclusive or negative conventional imaging.Methods Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with ^99mTc-MIBI and PET with ¹¹C-methionine. SUV_parathyroid/SUV_{cervical soft tissue} (target-to-background) and SUV_{parathyroid tissue}/SUV_{thyroid tissue} (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one.Results In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with ¹¹C-methionine PET and 17 (47%) with ^99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. ^99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with ^99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with ¹¹C-methionine PET. The highest SUV_parathyroid/SUV_{cervical soft tissue} ratio was found 10 min, and the highest SUV_{parathyroid tissue}/SUV_{thyroid tissue} ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection.Conclusion ¹¹C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and ^99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.     

Different uptake of 99mTc-ECD and 99mTc-HMPAO in the same brains: analysis by statistical parametric mapping

The purpose of this study was to investigate the differences between technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) uptake in the same brains by means of statistical parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female, mean age 62ᆠ years) using ^99mTc-ECD and ^99mTc-HMPAO single-photon emission tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7 days after onset of stroke. MRI showed no cortical infarctions. Infarctions in the pons (6 patients) and medulla (1), ischaemic periventricular white matter lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and sequential SPET techniques were used for ^99mTc-ECD and ^99mTc-HMPAO brain SPET, without repositioning of the patient. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the ^99mTc-ECD and ^99mTc-HMPAO SPET images were statistically analysed using statistical parametric mapping (SPM) 96 software. The difference between two groups was considered significant at a threshold of uncorrected P values less than 0.01. Visual analysis showed no hypoperfused areas on either ^99mTc-ECD or ^99mTc-HMPAO SPET images. SPM analysis revealed significantly different uptake of ^99mTc-ECD and ^99mTc-HMPAO in the same brains. On the ^99mTc-ECD SPET images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the left superior temporal lobe and in the superior region of the cerebellum. On the ^99mTc-HMPAO SPET images, relatively higher uptake was observed in the medial temporal lobes, thalami, periventricular white matter and brain stem. These differences in uptake of the two tracers in the same brains on SPM analysis suggest that interpretation of cerebral perfusion is possible using SPET with ^99mTc-ECD and ^99mTc-HMPAO.     

Effect of lamotrigine on cerebral blood flow in patients with idiopathic generalised epilepsy

Purpose The purpose of this study was to investigate the effects of the new anti-epileptic drug, lamotrigine, on cerebral blood flow by performing ^99mTc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) before and after medication in patients with drug-naive idiopathic generalised epilepsy.Methods Interictal ^99mTc-ECD brain SPECT was performed before drug treatment started and then repeated after lamotrigine medication for 4–5 months in 30 patients with generalised epilepsy (M/F=14/16, 19.3±3.4 years). Seizure types were generalised tonic-clonic seizure in 23 patients and myoclonic seizures in seven. The mean lamotrigine dose used was 214.1±29.1 mg/day. For SPM analysis, all SPECT images were spatially normalised to the standard SPECT template and then smoothed using a 12-mm full-width at half-maximum Gaussian kernel. The paired t test was used to compare pre- and post-lamotrigine SPECT images.Results SPM analysis of pre- and post-lamotrigine brain SPECT images showed decreased perfusion in bilateral dorsomedial nuclei of thalami, bilateral uncus, right amygdala, left subcallosal gyrus, right superior and inferior frontal gyri, right precentral gyrus, bilateral superior and inferior temporal gyri and brainstem (pons, medulla) after lamotrigine medication at a false discovery rate-corrected p<0.05. No brain region showed increased perfusion after lamotrigine administration.Conclusion Our study demonstrates for the first time the effect of lamotrigine on interictal cerebral perfusion in drug-naive idiopathic generalised epilepsy patients. In summary, lamotrigine medication was found to reduce perfusion in cortico-thalamo-limbic areas, the orbitofrontal cortex, and brainstem.     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia

Purpose Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response. Methods Seventeen women with FM (48 ± 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age. Results The VAS score for pain was 81.8 ± 4.2 before ketamine and 31.8 ± 27.1 after ketamine. Eleven patients were considered “good responders” to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%). Conclusion Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients.     

Efficacy of <Superscript>99m</Superscript>Tc pertechnetate and <Superscript>131</Superscript>I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo

Purpose There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects. Methods Biodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of ¹³¹I and ^99mTc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, ^99mTc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration. Results NIS-expressing neuroendocrine tumors strongly accumulated ¹³¹I and ^99mTc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of ¹³¹I or ^99mTc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of ^99mTc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of ^99mTc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons. Conclusions NIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.     

Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis

Purpose Brain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimotos thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of ^99mTc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent.Methods The diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent ^99mTc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere—frontal, temporal, parietal and occipital—and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry.Results As assessed by visual examination, ^99mTc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered.Conclusion These results show the high prevalence of brain perfusion abnormalities in euthyroid HT. These abnormalities are similar to those observed in cases of severe Hashimotos encephalopathy and may suggest a higher than expected involvement of CNS in thyroid autoimmune disease.     

Discrepant99mTc-ECD images of CBF in patients with subacute cerebral infarction: A comparison of CBF,CMRO2 and99mTc-HMPAO imaging

Three patients with subacute ischemic cerebral infarction examined by SPECT with^99mTc-ECD and PET within the same day showed signs of luxury perfusion in the subacute phase, which is between 9 to 20 days after the onset. A^99mTc-HMPAO SPECT study was also performed within 2 days of the ECD-SPECT study. ECD-SPECT images of three patients displayed a focal decreased uptake in the infarcted lesions, while in infarcted foci, there was almost equivalent or increased CBF compared to normal and unaffected areas, decreased CMRO₂, and high HMPAO uptake. The ECD-SPECT results were similar to those of CMRO₂ rather than CBF, though the HMPAO-SPECT image was similar to that of CBF. In one patient, HMPAO images revealed hyperfixation of the tracer. In the chronic phase and in the acute phase before 5 days after the onset, there were no discrepancies among the ECD-SPECT, CBF, HMPAO-SPECT, and CMRO₂ images. These observations indicated that^99mTc-ECD is a good indicator of damaged brain tissues in subacute ischemic infarction. They also suggested that^99mTc-ECD is a potential agent with which to evaluate cerebral tissue viability in some pathological states of cerebrovascular disease. The characteristics may be suitable for confirming the effects of thrombolytic therapy in acute ischemia, because these conditions often show signs of luxury perfusion when the therapy is successful.     

Combined study of99mTc-HMPAO SPECT and computerized electroencephalographic topography (CET) in patients with medically refractory complex partial epilepsy

For successful surgery for drug-resistant partial epilepsy the site of the seizure focus needs to be known exactly. The purpose of this study was to compare the evaluation of the regional cerebral blood flow (rCBF) (localization and degree of disturbances) by^99mTc-hexamethylpropylene-amineoxime (HMPAO) single photon emission computed tomography (SPECT) with computerized electroencephalographic topography (CET) and transmission computed X-ray tomography (CT) in partial epilepsy. The study included 20 patients with medically refractory complex partial seizures. Of the 20 patients included, 15 were studied interictally, four ictally and one in both states, interictally and ictally. ^99mTc-HMPAO SPECT detected rCBF changes in 95% of the patients. Interictal studies demonstrated focal areas of hypoperfusion in 93% of the patients. Ictal studies demonstrated an area of hyperperfusion in all patients. Blood flow disturbances in deeper structures of the brain, such as basal ganglia, could be detected. The areas with abnormal^99mTc-HMPAO uptake were concordant, in localization, with CET in 85% of the patients. Abnormal data with CT scans were found in only 45% of the patients. Focal lesions were found in 20% of the patients by CT scans. ^99mTc-HMPAO SPECT combined with CET may be a useful screening procedure prior to referral for invasive diagnostic procedures in future management of patients with medically refractory complex partial seizures.     

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of¹²³I-isopropyl-iodoam-phetamine (¹²³I-IMP) and^99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with¹²³I-IMP and^99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal^99mTc-HMPAO SPECT and abnormal¹²³I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on^99mTc-HMPAO in areas corresponding to defects on the¹²³I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,^99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on¹²³I-IMP. Crossed cerebellar diaschisis was found in 7 patients with^99mTc-HMPAO and was absent for both¹²³I-IMP and^99mTc-HMPAO in 3. We suggest that SPECT with⁹⁹mTc-HMPAO could show transient hyperemia not demonstrated by¹²³I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with^99mTc-HMPAO than with¹²³I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.     

Initial experience with SPECT of the brain using 99mTc-hexamethyl-propyleneamine oxime (99mTc-HM-PAO)

A recently developed ^99mTc radiocompound, hexamethyl-propyleneamine oxime (^99mTc-HM-PAO) exhibits favorable properties for regional cerebral tomograms in man utilizing conventional instrumentation (SPECT). Planar and tomographic studies using a rotating gamma camera equipped with a high sensitivity, low energy, collimator were performed in 5 normal subjects and 20 patients suffering from different cerebral diseases. SPECT abnormalities observed in patients with CVD, brain tumors and hydrocephalus were compared with results from X-ray CT. Our preliminary study demonstrates the feasibility of assessing regional brain perfusion using SPECT and a ^99mTc radiopharmaceutical which is lipid soluble and has a high extraction fraction in the brain.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

<Superscript>18</Superscript>F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with <Superscript>99m</Superscript>Tc-MIBI or <Superscript>99m</Superscript>Tc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients

Purpose

In this prospective study we compared the accuracy of ¹⁸F-fluorocholine PET/CT with that of ^99mTc-MIBI or^99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma.

Methods

Both ¹⁸F-fluorocholine PET/CT and ^99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either ¹⁸F-fluorocholine or ^99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3–6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis.

Results

All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78?±?0.34 mmol/l and parathormone (PTH) level of 196.5?±?236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with ¹⁸F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with ^99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of ¹⁸F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of ^99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although ¹⁸F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80?±?3.78 vs. 4.53?±?0.40) in the semiquantitative analysis, the difference was not significant (p?=?0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9?±?7.6 mm (median 15 mm, range 1–40 mm) and 1.71?±?1.86 g (median 1 g, range: 0.25–9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative ^99mTc-MIBI/tetrofosmin SPECT/CT and those with positive ^99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4?±?7.6 mm vs. 16.9?±?7.4 mm, respectively; p?=?0.042).

Conclusion

In this prospective study, ¹⁸F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to ^99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.

     

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of^99mTc-ECD. Hemispherical brain perfusion indices (BPI) for^99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for^99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between^99mTc-ECD BPI and^99mTc-HMPAO BPI and between^99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,^99mTc-ECD BPI was converted to¹³³Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of^99mTc-ECD were converted to rCBF maps using Lassen's correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for^99mTc-ECD SPET with those for^99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor of 2.6 gave nearly the same rCBF values for^99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for^99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in^99mTc-HMPAO studies is applicable to a^99mTc-ECD study for the measurement of rCBF without any blood sampling.     

Effect of linearization correction on statistical parametric mapping (SPM): A99mTc-HMPAO brain perfusion SPECT study in mild Alzheimer’s disease

OBJECTIVE: Statistical parametric mapping (SPM) was employed to investigate the regional decline in cerebral blood flow (rCBF) as measured by 99mTc-hexamethyl propylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) in mild Alzheimer's disease (AD). However, the role of the post reconstruction image processing on the interpretation of SPM, which detects rCBF pattern, has not been precisely studied. We performed 99mTc-HMPAO SPECT in mild AD patients and analyzed the effect of linearization correction for washout of the tracer on the detectability of abnormal perfusion. METHODS: Eleven mild AD (NINCDS-ADRDA, male/female, 5/6; mean+/-SD age, 70.6+/-6.2 years; mean+/-SD mini-mental state examination score, 23.9+/-3.41; clinical dementia rating score, 1) and eleven normal control subjects (male/female, 4/7; mean+/-SD age, 66.8+/-8.4 years) were enrolled in this study. 99mTc-HMPAO SPECT was performed with a four-head rotating gamma camera. We employed linearization uncorrected (LU) and linearization corrected (LC) images for the patients and controls. The pattern of hypoperfusion in mild AD on LU and LC images was detected by SPM99 applying the same image standardization and analytical parameters. A statistical inter image-group analysis (LU vs. LC) was also performed. RESULTS: Clear differences were observed between the interpretation of SPM with LU and LC images. Significant hypoperfusion in mild AD was found on the LU images in the left posterior cingulate gyrus, right precuneus, left hippocampus, left uncus, and left superior temporal gyrus (cluster level, corrected p < 0.005). With the LC images, significant hypoperfusion in AD was found only in the bilateral posterior cingulate gyrus and left precuneus (cluster level, corrected p < 0.005). A pattern of greater rCBF distribution at the high flow cortices and low flow cortices was observed on LC and LU images, respectively, in the case of both controls and mild AD patients. CONCLUSION: Hippocampal hypoperfusion could be detected by means of SPM in the LU images but not in the LC images. The results of SPM may vary in 99mTc-HMPAO SPECT with or without linearization correction, which should be carefully evaluated when interpreting the pattern of rCBF changes in mild Alzheimer's disease.     

Simultaneous acquisition of <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors

Objective

Simultaneous acquisition of ^99mTc and ¹²³I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors.

Methods

10-ml cylindrical syringes contained about 37 MBq ^99mTc-tetrofosmin (^99mTc-TF) or 37 MBq ¹²³I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (¹²³I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP to assess the influence of ^99mTc upscatter and ¹²³I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP. Two 1-ml syringes contained 105 MBq ^99mTc-labeled hexamethylpropyleneamine oxime (^99mTc-HMPAO) and 35 MBq ¹²³I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹²³I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq ^99mTc-HMPAO and 35 MBq ¹²³I-FP-CIT.

Results

The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of ¹²³I-BMIPP exhibited fewer radioactive counts for 300 MBq ^99mTc-TF without scatter correction (SC) in 125–150 keV. There was no upscatter contamination of ^99mTc-TF in 150–175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq ^99mTc-TF without SC in 125–150 keV. In the rats, myocardial images and radioactive counts of ^99mTc-TF with the dual tracer were identical to those of the ^99mTc-TF single injection. Downscatter contamination of ¹²³I-FP-CIT was 4.2 % without SC in 125–150 keV. In the first injection of ^99mTc-HMPAO and second injection of ¹²³I-FP-CIT, brain images and radioactive counts of ^99mTc-HMPAO with the dual tracer in normal mice also were the similar to those of the ^99mTc-HMPAO single injection. In the first injection of ¹²³I-FP-CIT and second injection of ^99mTc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the ¹²³I-FP-CIT single injection.

Conclusions

Dual-tracer imaging of ^99mTc- and ¹²³I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of ^99mTc-labeled radiotracers relative to ¹²³I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of ^99mTc- and ¹²³I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

     

Postoperative assessment of cerebral blood flow in subarachnoid haemorrhage by means of99mTc-HMPAO tomography

Regional hypoperfusion is a very frequent complication of subarachnoid haemorrhage (SAH), being related to vasospasm in the majority of cases. Twenty-six patients who were admitted for SAH underwent follow-up with technetium-99m hexamethylpropylene amine oxime single photon emission tomography (SPECT) 3 and 8 days after surgery. Fifteen patients of these had one more examination 15 days after surgery. The degree of hypoperfusion was quantified using an index of asymmetry which allow the comparison of two symmetrical regions of interest (ROIs) on the transaxial slice which presented the greatest perfusion defect. Comparison of CT data, transcranial Doppler data and clinical signs with the perfusion as quantified by^99mTc-HMPAO SPECT indicates that a difference in counts of less than 10% between the two symmetrical ROIs is of no diagnostic value. Follow-up of the brain perfusion clearly shows that the most pronounced hypoperfusion was observed just after surgery, with progressive normalization at 8 and 15 days after surgery.^99mTc-HMPAO SPECT performed 8 days after surgery allows prediction of the clinical outcome. For these reasons,^99mTc-HMPAO SPECT, which is the only method for follow-up of cerebral perfusion in routine clinical practice, should be the first examination to be performed after surgery in patients with SAH.