Impact of age on myocardial uptake of 123I-mIBG in older adult subjects without coronary heart disease

Background

The purpose of this study was to examine the relationship between myocardial uptake of ¹²³I-mIBG and age in older normal adult subjects.

Methods

94 subjects (age 29-82, mean 58.5) without coronary heart disease were studied. All subjects underwent early and delayed planar and 4-hour SPECT ¹²³I-mIBG imaging. ¹²³I-mIBG uptake was quantified as heart/mediastinum ratio on planar images (H/M _p) and on SPECT images (H/M _s) reconstructed by filtered backprojection, ordered subsets-expectation maximization (OSEM), and OSEM with compensation for collimator septal penetration (DSP). Relationships between age and ¹²³I-mIBG uptake were examined by correlation analysis, t-tests, and analysis of variance.

Results

There was no significant correlation between age and H/M _p, reflecting comparable increases in activity in the two regions of interest with age. Results on SPECT analyses were comparable, with no significant correlation between age and H/M _s. Using DSP, ¹²³I-mIBG H/M _s was significantly higher in subjects ≥70 of age compared with younger subjects.

Conclusions

Both cardiac and background uptake of ¹²³I-mIBG increase with age in older subjects without coronary heart disease, resulting in stability of H/M results (planar and SPECT). This study suggests that prognostic analyses of quantitative ¹²³I-mIBG uptake in patients with heart disease do not require adjustment for patient age.     

123I-mIBG Scintigraphy to predict risk for adverse cardiac outcomes in heart failure patients: Design of two prospective multicenter international trials

Background  ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) consists of two identical prospective open-label, multicenter, phase 3 studies (MBG311 and MBG312) evaluating the prognostic usefulness of ¹²³I-mIBG scintigraphy for identifying subjects with heart failure who will experience a major adverse cardiac event. Methods  Subjects with NYHA class II and III heart failure and left ventricular ejection fraction ≤35% were eligible for the trials. Subjects underwent planar and SPECT ¹²³I-mIBG myocardial imaging, as well as echocardiography and gated SPECT ^99mTc-tetrofosmin myocardial perfusion imaging. Subjects are then monitored on a regular basis for 2 years. Time to first occurrence of one of the following—NYHA class progression; potentially life-threatening arrhythmic event (including ICD discharge); or cardiac death, as verified by an independent adjudication panel—will be analyzed in comparison to quantitative parameters derived from ¹²³I-mIBG imaging. The primary efficacy analysis will employ the heart/mediastinum ratio on 4-hour delayed planar imaging, while secondary efficacy analyses will examine quantitative results from both planar and SPECT ¹²³I-mIBG images, as well as from ^99mTc-tetrofosmin SPECT and echocardiography. Conclusion  The results of the ADMIRE-HF trials will provide prospective validation of the potential role of ¹²³I-mIBG scintigraphy in assessing prognosis and developing management strategies for patients with heart failure. Funding Source: GE Healthcare.     

Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability

Purpose

The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and ¹²³I-metaiodobenzylguanidine (¹²³I-mIBG) myocardial scintigraphy.

Methods

The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and ¹²³I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by ¹²³I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13.

Results

The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and ¹²³I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, ¹²³I-mIBG scintigraphy showed CAN.

Conclusion

The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and ¹²³I-mIBG scintigraphy for the assessment of CAN was observed.     

Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic sudden cardiac death

Sudden cardiac death (SCD) accounts for about ½ of all cardiovascular deaths, in most cases the result of a lethal ventricular arrhythmia. Patients considered at risk are often treated with an implantable cardiac defibrillator (ICD), but current criteria for device use, based largely on left ventricular ejection fraction (LVEF), leads to many patients receiving ICDs that they do not use, and many others not receiving ICDs but who suffer SCD. Thus, better methods of identifying patients at risk for SCD are needed, and radionuclide imaging offers much potential. Recent work has focused on imaging of cardiac autonomic innervation. ¹²³I-mIBG, a norepinephrine analog, is the tracer most studied, and a variety of positron emission tomographic tracers are also under investigation. Radionuclide autonomic imaging may identify at-risk patients with ischemic coronary artery disease, particularly following myocardial infarction and in the setting of hibernating myocardium. Most studies have been done in the setting of congestive heart failure (CHF), with a recent large multicenter study of patients with advanced disease, typically at high risk of SCD, showing that ¹²³I-mIBG can identify a low risk subgroup with an extremely low incidence of lethal ventricular arrhythmias and cardiac death, therefore, perhaps not requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive of lethal arrhythmias/cardiac death than LVEF and New York Heart Association class, as well as various ECG parameters. Autonomic imaging will likely play an important role in the advancement of cardiac molecular imaging.     

Radionuclide imaging of cardiac autonomic innervation

Cardiac autonomic function plays a crucial role in health and disease, with abnormalities both reflecting the severity of the disease and contributing specifically to clinical deterioration and poor prognosis. Radiotracer analogs of the sympathetic mediator norepinephrine have been investigated extensively, and are at the brink of potential widespread clinical use. The most widely studied SPECT tracer, I-123 metaiodobenzylguanidine (¹²³I-mIBG) has consistently shown a strong, independent ability to risk stratify patients with advanced congestive heart failure. Increased global cardiac uptake appears to have a high negative predictive value in terms of cardiac events, especially death and arrhythmias, and therefore and may have a role in guiding therapy, particularly by helping to better select patients unresponsive to conventional medical therapies who would benefit from device therapies such as an ICD (implantable cardioverter defibrillator), CRT (cardiac resynchronization therapy), LVAD (left ventricular assist device), or cardiac transplantation. Cardiac autonomic imaging with SPECT and PET tracers also shows potential to assess patients following cardiac transplant, those with primary arrhythmic condition, coronary artery disease, diabetes mellitus, and during cardiotoxic chemotherapy. Radiotracer imaging of cardiac autonomic function allows visualization and quantitative measurements of underlying molecular aspects of cardiac disease, and should therefore provide a perspective that other cardiac tests cannot.     

I-123-<Emphasis Type="Italic">m</Emphasis>IBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study

Purpose Single-center experiences have shown that myocardial meta-iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF) patients. To verify these observations using a rigorous clinical trial methodology, a retrospective review and prospective quantitative reanalysis was performed on a series of cardiac ¹²³I-mIBG scans acquired during a 10-year period at six centers in Europe. Methods ¹²³I-mIBG scans obtained on 290 HF patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993 to 2002 were reanalyzed using a standardized methodology to determine the heart-to-mediastinum ratio (H/M) on delayed planar images. All image results were verified by three independent reviewers. Major cardiac events [MCEs; cardiac death, cardiac transplant, potentially fatal arrhythmia (including implantable cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed by an adjudication committee. Results MCEs occurred in 67 patients (26%): mean H/M ratio was 1.51 ± 0.30 for the MCE group and 1.97 ± 0.54 for the non-MCE group (p < 0.001). Two-year event-free survival using an optimum H/M ratio threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF as the only significant predictors of MCE. Using the lower and upper H/M quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event-free survival rates were 52% and 98%, respectively. Among patients with LVEF ≤ 35% and H/M ≥ 1.75 (n = 73), there were nine MCEs because of progressive HF and only one because of an arrhythmia. Conclusion Application of a clinical trial methodology via the retrospective reanalysis of ¹²³I-mIBG images confirms the previously reported prognostic value of this method in HF patients, including potential identification of a quantitative threshold for low risk for cardiac mortality and potentially fatal ventricular arrhythmias.     

Influence of myocardial region of interest definition on quantitative analysis of planar 123I-mIBG images

Purpose

In planar ¹²³I-mIBG myocardial imaging, definition of the heart region of interest (ROI) is a critical step in quantifying uptake. The present study evaluated the impact of changes in heart ROI size on quantitative results in subjects with good and poor uptake.

Methods

Reference irregular whole-heart and square upper mediastinum ROIs were defined visually on 531 planar ¹²³I-mIBG images. Based on the reference heart ROI, an automated program created two other ROIs: one larger (+1 pixel) and one smaller (?1 pixel), the stated numbers representing the spacing intervals between each epicardial boundary pixel. Two additional smaller ROIs (?2 and ?3 pixels) were drawn for the 100 images (19 %) with a heart/mediastinum (H/M) ratio ≤1.30. The number of pixels, the counts per pixel, and the H/M ratio for each heart ROI were calculated and compared to that in the reference ROI. Washout rate and changes as a function of ROI size were also calculated for 110 subjects who had both early and late images.

Results

The mean changes in heart ROI size ranged from +19.0 % for the +1 pixel to ?44.4 % for the ?3 pixels ROI. For the +1 and ?1 pixel ROIs, mean relative counts per pixel changes were ?1.2 % and +0.7 %, respectively, with corresponding ranges of change in the H/M ratio of ?0.12 to +0.05 and ?0.05 to +0.11. For scans with H/M ratio ≤1.30, mean relative counts per pixel changes were 0, 0, ?0.7 %, and ?1.4 % for the four ROIs, with range of change in the H/M ratio from ?0.13 to +0.05. Mean washout rates were almost identical for the reference ROIs (45.0 %) and the +1 pixel and ?1 pixel heart ROIs (44.9 % and 45.1 %, respectively).

Conclusion

Significant changes in the size of the best visually defined heart ROI produce minimal, clinically inconsequential changes in the H/M ratio and washout rate, even in subjects with significantly reduced myocardial uptake of ¹²³I-mIBG.     

Cardiac applications of 123I-mIBG imaging

Cardiac autonomic innervation plays a key role in maintaining hemodynamic and electrophysiologic harmony. Cardiac sympathetic function is adversely altered in many disease states, such as congestive heart failure, myocardial ischemia, and diabetes. (123)I-mIBG, a sympathetic neurotransmitter radionuclide analog, aids in the detection of sympathetic innervation abnormalities and can be imaged with planar and single-photon emission computed tomographic techniques. Cardiac (123)I-mIBG uptake can be assessed by the heart mediastinal ratio (H/M), tracer washout rate, and focal uptake defects. These parameters have been widely studied and shown to correlate strongly and independently with congestive heart failure progression, cardiac arrhythmias, cardiac death, and all-cause mortality. There is accumulating evidence that (123)I-mIBG imaging can help to monitor a patient's clinical course and response to therapy. The ability to predict potentially lethal ventricular arrhythmias promises to help more accurately select patients for implantable cardioverter defibrillators, limiting unnecessary devices and identifying additional patients at risk who do not meet current guidelines. (123)I-mIBG shows potential to help determine whether greater risk and usually more expensive ventricular assist device therapies or cardiac transplantation might be needed. Although more investigation in larger populations is needed to strengthen previous findings, cardiac (123)I-mIBG imaging shows promise as a new technique for recognizing and following potentially life-threatening cardiac conditions.     

The utility of ADMIRE-HF risk score in predicting serious arrhythmic events in heart failure patients: Incremental prognostic benefit of cardiac 123I-mIBG scintigraphy

Background

A minority of heart failure (HF) patients who undergo implantable cardioverter defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD) receive device therapy. Whether the addition of mIBG scintigraphy to conventional markers of arrhythmic risk can provide incremental risk stratification in HF patients has not been investigated.

Methods

We identified 778 patients from the ADMIRE-HF study with LVEF < 35% and class II or III HF symptoms who did not have an ICD at the time of enrollment. Patients were followed up prospectively (median = 17 months) for occurrence of arrhythmic events (ArE). Heart-to-mediastinum ratio (HMR) was determined as a measure of relative myocardial sympathetic nerve activity at baseline using ¹²³I-mIBG. The primary endpoint was the first occurrence of ArE: a composite of SCD, appropriate ICD therapy, resuscitated cardiac arrest or sustained ventricular tachycardia. Multivariate regression was used to determine independent predictors of ArE and to derive a risk score for ArE prediction. The score was used to group patients according to their risk for ArE. Integrated discrimination improvement (IDI) was used to quantify improvement in risk assessment with addition of HMR.

Results

ArE occurred in 54 patients (6.9%). ArE predictors were: HMR < 1.6 (HR 3.5, 95% CI [1.52-8], P = .02), LVEF < 25% (HR 2.0, 95% CI [1.28-3.05], P = .04) and SBP < 120 (HR 1.2, 95% CI [1.03-1.39], P = .02). Event rates in the low-, intermediate-, and high risk groups were 2, 10 and 16%, respectively (P = .001). The score significantly improved risk prediction (IDI = 45%, P 0.03).

Conclusion

¹²³I-mIBG significantly provides incremental risk stratification for ArE in HF patients.     

Assessment of global cardiac I-123 MIBG uptake and washout using volumetric quantification of SPECT acquisitions

Background

Assessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated.

Methods

54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images.

Results

Cardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R ²?=?0.36; delayed R ² =0.43) and myocardial wall (early R ²?=?0.28; delayed R ²?=?0.37). Lung washout was an explanatory variable of organ washout of the heart (heart R ²?=?0.38; myocardial wall R ²?=?0.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851).

Conclusion

By applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I-123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices.     

Iodine-123N- methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors

Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [¹²³I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereo selectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of >2.5:1 between 10 and 30 min, making SPET imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [¹²³I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [¹²³I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease.     

Doxorubicin-induced cardiac neurotoxicity: Study with iodine 123-labeled metaiodobenzylguanidine scintigraphy

Background

Iodine 123-labeled metaiodobenzylguanidine (¹²³I-MIBG) can be used to generate a scintigraphic image of the adrenergic nervous innervation of the heart.

Methods and Results

To test the hypothesis that doxorubicin may lead to damage of cardiac neurons, we examined 37 patients with various malignant neoplasms, 14 of whom were on therapy with doxorubicin. All patients were examined with ¹²³I-MIBG scintigraphy and radionuclide ventriculography. Cardiac ¹²³I-MIBG uptake was assessed by means of a heart to mediastinum activity ratio (H/M). Left ventricular ejection fraction was not different in patients with or without doxorubicin. In patients receiving doxorubicin, the H/M ratio was significantly lower (1.73±0.25 vs 2.13±0.25, p<0.001) and correlated with doxorubicin cumulative dose (r=?0.51, p<0.001). By using a H/M ratio of 1.73 as a cutoff point, ¹²³I-MIBG uptake was abnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p<0.001). In 10 patients initially not receiving doxorubicin, ¹²³I-MIBG scintigraphy was repeated after receiving 236±47 mg/m² of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 of 10 patients.

Conclusion

¹²³I-MIBG cardiac uptake decreases in a doxorubicin dose-dependent way, indicating a cardiac adrenergic neurotoxic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.     

Relationship between quantitative cardiac neuronal imaging with 123I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

Purpose

Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between ¹²³I-mIBG imaging findings and hospitalization.

Methods

Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using ¹²³I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression.

Results

During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p?=?0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 – 2.0; p?=?0.02).

Conclusion

The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.     

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.     

Iodine-123 metaiodobenzylguanidine in the assessment of late cardiac effects from cancer therapy

Recognition of adverse late cardiac effects from cancer therapy may enable identification of patients with risk of cardiotoxicity upon cancer retreatment. In this study the feasibility of using iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) heart scintigraphy to detect abnormalities of the myocardial adrenergic neurone function in the late period after cancer therapy was evaluated in relation to the left ventricle ejection fraction (LVEF) in 18 cancer patients: 11 had undergone thoracic irradiation involving the heart, in five cases in combination with anthracycline therapy, 11–228 months (median 60 months) before radionuclide tests, while seven had not received previous anthracycline and/or radiotherapy (controls). The¹²³I-MIBG cardiac uptake, expressed as a heart-to-mediastinum ratio on planar images after 4 h, ranged from 1.21 to 1.76 (median 1.56) in cancer therapy patients, which was significantly decreased (P=0.0006) in comparison with controls (range 1.81–2.06, median 1.9). The myocardial¹²³I-MIBG washout, calculated from planar images after 15 min and 4 h, and LVEF also showed significant differences, but with some overlap in individual cases. In cancer therapy patients, cardiac abnormalities seen on planar images and additional single-photon emission tomographic images varied from focal defects to diffusely reduced myocardial uptake. It is concluded that¹²³I-MIBG heart scintigraphy, which is able to identify cardiac adrenergic neurone abnormalities in the follow-up period after cancer therapy, may help to identify relapsed patients who are at increased risk of developing cardiotoxicity during retreatment with cardiotoxic therapy modalities.This paper was presented as an oral communication at the European Association of Nuclear Medicine Congress in Brussels, 1995     

A new model for separation between brain dopamine and serotonin transporters in <Superscript>123</Superscript>I-β-CIT SPECT measurements: normal values and sex and age dependence

¹²³I--CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since ¹²³I--CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble ¹²³I--CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for ¹²³I--CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1–2 h and DAT imaging at 20–24 h; (2) blocking the 5HTT re-uptake with citalopram renders ¹²³I--CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved ¹²³I--CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT.     

Nuclear imaging in cardiac amyloidosis

Amyloidosis is a disease characterized by depositions of amyloid in organs and tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis is a debilitating disease and can lead to arrhythmias, deterioration of heart function and even sudden death. We reviewed PubMed/Medline, without time constraints, on the different nuclear imaging modalities that are used to visualize myocardial amyloid involvement. Several SPECT tracers have been used for this purpose. The results with these tracers in the evaluation of myocardial amyloidosis and their mechanisms of action are described. Most clinical evidence was found for the use of ¹²³I-MIBG. Myocardial defects in MIBG activity seem to correlate well with impaired cardiac sympathetic nerve endings due to amyloid deposits. ¹²³I-MIBG is an attractive option for objective evaluation of cardiac sympathetic level and may play an important role in the indirect measurement of the effect of amyloid myocardial infiltration. Other, less sensitive, options are ^99mTc-aprotinin for imaging amyloid deposits and perhaps ^99mTc-labelled phosphate derivatives, especially in the differential diagnosis of the aetiology of cardiac amyloidosis. PET tracers, despite the advantage of absolute quantification and higher resolution, are not yet well evaluated for the study of cardiac amyloidosis. Because of these advantages, there is still the need for further research in this field.     

Clinical evaluation of 99mTc-pyrophosphate myocardial emission computed tomography: Comparison with planar imaging

To depict the three-dimensional distribution of ^99mTc-pyrophosphate in the heart, emission computed tomography (ECT) was performed, following the conventional planar imaging, in 32 cases with suspected acute myocardial infarction (AMI). There were 23 cases with evidence of AMI, 7 with unstable angina (UA), and 2 with dilated cardiomyopathy (DCM). While the planar images showed discrete cardiac activity in only 11 of the 23 cases (48%) with AMI, the ECT images delineated focal myocardial uptake clearly in 20 of them (87%). On the other hand, the ECT images revealed cardiac blood-pool activity without significant myocardial uptake in all cases with UA and DCM in which the planar images showed diffuse activity. Thus, the ECT imaging of ^99mTc-pyrophosphate seems to be a valuable technique for assessing the presence and localization of myocardial necrosis, especially in cases showing diffuse cardiac activity in the planar imaging.     

Radioiodinated 4-iodo-L-meta-tyrosine, a system L selective artificial amino acid: molecular design and transport characterization in Chinese hamster ovary cells (CHO-K1 cells)

IntroductionHigh expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of ¹⁴C(U)-l-tyrosine (¹⁴C-Tyr), ¹²⁵I-4-iodo-l-meta-tyrosine (4-¹²⁵I-mTyr), ¹²⁵I-6-iodo-l-meta-tyrosine (6-¹²⁵I-mTyr), ¹²⁵I-3-iodo-α-methyl-l-tyrosine (¹²⁵I-IMT) and ¹²⁵I-3-iodo-l-tyrosine (3-¹²⁵I-Tyr) using Chinese hamster ovary cells (CHO-K1).MethodsCells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na⁺ at 37°C or 4°C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na⁺-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na⁺-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN₃ and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and l- and d-isomers of natural amino acids.Results¹⁴C-Tyr exhibited affinity for systems L, A and ASC. 4-¹²⁵I-mTyr and 3-¹²⁵I-Tyr exhibited high specificity for system L, whereas 6-¹²⁵I-mTyr and ¹²⁵I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-¹²⁵I-mTyr was markedly reduced by incubation at 4 °C, and was not significantly inhibited by NaN₃, DNP, PAH or TEA. The inhibition profiles of the l- and d-isomers of natural amino acids indicated that system L mediates the transport of 4-¹²⁵I-mTyr.Conclusions4-¹²⁵I-mTyr exhibited the greatest system L specificity (93.46±0.13%) of all of the tested amino acids.     

Simultaneous dual-isotope imaging based on an artificial neural network for evaluating myocardial perfusion and fatty acid metabolism

Background

We contrived a scatter correction method based on an artificial neural network (ANN) and applied it to the simultaneous evaluation of myocardial perfusion and fatty acid metabolism in single-photon emission computed tomography (SPECT).

Methods

The count data of three energy windows were used as inputs of the ANN. The count ratios of the estimated primary-to-total photons for ^99mTc and ¹²³I, which were used to reconstruct ^99mTc and ¹²³I images, were calculated using the ANN. In a phantom study, single- and dual-isotope imaging with ^99mTc/¹²³I and ²⁰¹Tl/¹²³I was performed by means of a cardiac phantom simulating patients with and without obesity. In a human study, five normal volunteers and ten patients with myocardial infarction underwent myocardial perfusion and fatty acid metabolism imaging with single and dual SPECT with combinations of ^99mTc-methoxyisobutylisonitrile/¹²³I-beta-methyl(p-iodophenyl)pentadecanoic acid (BMIPP) and ²⁰¹Tl/¹²³I-BMIPP as tracers.

Results

Technetium-99m yielded more homogeneous images than ²⁰¹Tl because of the lower degree of photon attenuation, especially in the condition of obese patients, resulting in clearer visualization of the perfusion-metabolism mismatch. Dual ^99mTc/¹²³I SPECT offered comparable images with single SPECT in assessing myocardial damage.

Conclusions

The method effectively separated ^99mTc and ¹²³I primary photons and proved applicable to ^99mTc/¹²³I dual-isotope myocardial SPECT.