Single Photon Emission Computed Tomography Scans Research Articles

ACCURACY OF SPECT IMAGING FOR ARTHROSCOPICALLY CONFIRMED MENISCAL TEARS IN PATIENTS WITH ACUTE KNEE PAIN AND NO RADIOGRAPHIC ARTHRITIS

Purpose: To evaluate the accuracy of single photon emission computed tomography (SPECT) compared with arthroscopy in the diagnosis of acute knee pain due to meniscal tear. Methods: Patients with knee pain that persisted for less than six months with normal plain radiographs that had arthroscopic surgery following SPECT scan were included. The main scintigraphic criterion for diagnosing a tear of the meniscus was tibial plateau activity on the planar image with at least a half crescent of peripheral tibial plateau uptake. The accuracy of SPECT in detecting meniscal tears was calculated according to the arthroscopic findings as the gold standard. Results: There were 68 patients in the study (46 males and 22 females). The mean age was 45.3 (17–72) years and the mean time between SPECT scan and surgery was 3.5 (1–6) months. The overall sensitivity of SPECT was 90%, specificity 70%, NPV 54%, PPV 95% and accuracy 87%. Conclusion: SPECT was found to be an accurate imaging technique in the diagnosis of symptomatic meniscal tears in patients with acute knee pain and unremarkable plain radiographs. Thus, SPECT may be helpful in selecting candidates for arthroscopy.

Conventional SPECT Versus 3D Thresholded SPECT Imaging in the Diagnosis of ADHD: A Retrospective Study.

Brain single photon emission CT (SPECT) scans indirectly show functional activity via measurement of regional cerebral blood flow. In conventional SPECT scans, the typical tomographic slices are produced. In three-dimensional thresholded SPECT scans, pixels representing activity below a certain threshold are discarded. A retrospective analysis of 427 patients shows that three-dimensional thresholded SPECT scans yield a sensitivity for predicting clinical attention deficit hyperactivity disorder of 54% [95% confidence interval (CI), 46%-61%; specificity, 76%; 95% CI, 71%-81%] compared with 4% sensitivity [95% CI, 2%-8%; specificity, 97%; 95% CI, 94%-98%] for conventional SPECT scans. For 170 of the patients originating from a general psychiatry practice, conventional SPECT showed 10% sensitivity (95% CI, 4%-23%) and 98% specificity (95% CI, 93%-99%), whereas three-dimensional thresholded SPECT showed 83% sensitivity (95% CI, 68%-91%) and 77% specificity (95% CI, 69%-83%). These findings indicate that a much stronger signal is obtained when the three-dimensional thresholded SPECT scan is performed rather than the conventional SPECT scan in detecting attention deficit hyperactivity disorder and suggest similar results may be obtained for other psychiatric disorders.

Hot water epilepsy: Phenotype and single photon emission computed tomography observations.

We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT). Five men (mean age: 27.0 ΁ 5.8 years) with HWE were subjected to MRI of brain, video-EEG studies, and SPECT scan. These were correlated with phenotypic presentations. Seizures could be precipitated in three patients with pouring of hot water over the head and semiology of seizures was suggestive of temporal lobe epilepsy. Ictal SPECT showed hyperperfusion in: left medial temporal — one, left lateral temporal — one, and right parietal — one. Interictal SPECT was normal in all five patients and did not help in localization. MRI and interictal EEG was normal in all the patients. The clinical and SPECT studies suggested temporal lobe as the seizure onset zone in some of the patients with HWE.

Lung tumors: Early and delayed ratio of 99mTc-methoxy-2-isobutylisonitrile accumulation

Currently used radiopharmaceuticals are nonspecific and most of them are accumulated by benign tumors as well as inflammatory lesions, abscess or granulomatous lesions. Some factors such as the choice of radiopharmaceutical applied, histopathologic type of tumor, its size, location or previous tumor treatment could influence tumor imaging sensitivity. The aim of this study was to investigate accumulation of 99mTc-methoxy-2-isobutylisonitrile (99mTc-MIBI) by counting early/delayed uptake and release of this radiopharmaceutical inside lung tumors and evaluating possible factors which could be involved in its accumulation. Two-phase 99mTc-methoxy-2-isobutylisonitrile single photon emission computed tomography scan (early and delayed scan) was performed in 60 patients with lung tumors (the group 1 - 30 benign, and the group 2 - 30 malignant tumors). We calculated the uptake ratio on early (early ratio - ER), delayed images (delayed ratio - DR) and retention index (RI). Individual influence of etiology, diameter, localization, and histological type on uptake/release values was evaluated with regression analysis. The values of ER and DR were significantly different in both groups (p < 0.01), showing lower values in benign vs malignant lung tumors (ER 1.36 ± 0.094 and DR 1.25 ± 0.089 vs ER = 1.93 ± 0.106 and DR = 1.7 ± 0.095 respectively). Tumor size showed a significant influence on the change of ER and DR values (p < 0.01), with greater uptake in tumors > 3 cm. RI values showed no significance between the two groups (P > 0.05). The uptake ratio of 99mTc-methoxy-2-isobutylisonitrile could be a useful index in differentiating lung tumors, while RI has no influence on this. Among the evaluated factors, ER and DR values are significantly influenced only by the diameter of lung tumor, while localization or different histological types between the groups has no influence on this.

Differences of various region-of-interest methods for measuring dopamine transporter availability using 99mTc-TRODAT-1 SPECT.

This study was to investigate whether various region-of-interest (ROI) methods for measuring dopamine transporter (DAT) availabilities by single photon emission computed tomography (SPECT) are statistically different, whether results of medical research are thereby influenced, and causes of these differences. Eighty-four healthy adults with 99mTc-TRODAT-1 SPECT and magnetic resonance imaging (MRI) scans were included. Six major analysis approaches were compared: (1) ROI drawn on the coregistered MRI; (2) ROIs drawn on the SPECT images; (3) standard ROI templates; (4) threshold-ROIs; (5) atlas-based mappings with coregistered MRI; and (6) atlas-based mappings with SPECT images. Using the atlas-based approaches we assessed the influence of striatum ROIs by slice-wise and voxel-wise comparisons. In (5) and (6), three partial-volume correction (PVC) methods were also explored. The results showed that DAT availabilities obtained from different methods were closely related but quite different and leaded to significant differences in determining the declines of DAT availability per decade (range: 5.95–11.99%). Use of 3D whole-striatum or more transverse slices could avoid biases in measuring the striatal DAT declines per decade. Atlas-based methods with PVC may be the preferable methods for medical research.

Improved Outcomes Using Brain SPECT-Guided Treatment Versus Treatment-as-Usual in Community Psychiatric Outpatients: A Retrospective Case-Control Study

Brain single-photon emission computed tomography (SPECT) scans indirectly show functional activity via measurement of regional cerebral blood flow. Thirty patients at a community-based psychiatric clinic underwent brain SPECT scans. Changes in scoring of before-treatment and after-treatment scans correlated well with changes in patient Global Assessment of Functioning (GAF) scores before treatment and after treatment. Patients were retrospectively matched with controls with similar diagnoses and pretreatment GAF scores, and those who underwent SPECT-guided treatment improved significantly more than the control patients.

Automatic classification and prediction models for early Parkinson’s disease diagnosis from SPECT imaging

Early and accurate diagnosis of Parkinson’s disease (PD) is important for early management, proper prognostication and for initiating neuroprotective therapies once they become available. Recent neuroimaging techniques such as dopaminergic imaging using single photon emission computed tomography (SPECT) with 123I-Ioflupane (DaTSCAN) have shown to detect even early stages of the disease. In this paper, we use the striatal binding ratio (SBR) values that are calculated from the 123I-Ioflupane SPECT scans (as obtained from the Parkinson’s progression markers initiative (PPMI) database) for developing automatic classification and prediction/prognostic models for early PD. We used support vector machine (SVM) and logistic regression in the model building process. We observe that the SVM classifier with RBF kernel produced a high accuracy of more than 96% in classifying subjects into early PD and healthy normal; and the logistic model for estimating the risk of PD also produced high degree of fitting with statistical significance indicating its usefulness in PD risk estimation. Hence, we infer that such models have the potential to aid the clinicians in the PD diagnostic process.

SPECT/CT and pulmonary embolism

Acute pulmonary embolism (PE) is diagnosed either by ventilation/perfusion (V/P) scintigraphy or pulmonary CT angiography (CTPA). In recent years both techniques have improved. Many nuclear medicine centres have adopted the single photon emission CT (SPECT) technique as opposed to the planar technique for diagnosing PE. SPECT has been shown to have fewer indeterminate results and a higher diagnostic value. The latest improvement is the combination of a low-dose CT scan with a V/P SPECT scan in a hybrid tomograph. In a study comparing CTPA, planar scintigraphy and SPECT alone, SPECT/CT had the best diagnostic accuracy for PE. In addition, recent developments in the CTPA technique have made it possible to image the pulmonary arteries of the lungs in one breath-hold. This development is based on the change from a single-detector to multidetector CT technology with an increase in volume coverage per rotation and faster rotation. Furthermore, the dual energy CT technique is a promising modality that can provide functional imaging in combination with anatomical information. Newer high-end CT scanners and SPECT systems are able to visualize smaller subsegmental emboli. However, consensus is lacking regarding the clinical impact and treatment. In the present review, SPECT and SPECT in combination with low-dose CT, CTPA and dual energy CT are discussed in the context of diagnosing PE.

Movement Disorder Society Unified Parkinson Disease Rating Scale experiences in daily living: Longitudinal changes and correlation with other assessments

The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the goals of improving instructions and definitions, more accurately evaluating milder features, and assessing patient-reported outcomes and nonmotor features. To date, no study has evaluated longitudinal changes in components of the MDS-UPDRS over time or correlated these with changes in other scales of various symptoms. We assessed Parts I and II of the MDS-UPDRS (non-Motor and Motor Experiences of Daily Living [nM-EDL, M-EDL]) as well as a number of other scales of motor, cognitive and behavioral function in a large population of patients (n = 383) with early- to mid-stage Parkinson's disease (PD) who had previously participated in a trial of a putative disease-modifying agent. Both parts of a MDS-UPDRS showed significant change over the 3-year follow-up period, with M-EDL scores declining to a greater extent than nM-EDL. Both the scores and their changes over time correlated relatively well with other rating scales of similar disease aspects. Modest correlations with the original version of the UPDRS supported the increased attention to nonmotor symptoms as well as milder levels of severity in the MDS-UPDRS. The M-EDL was much more sensitive to change over time in these early- to mid-stage patients than the original UPDRS Activities of Daily Living (ADL) scale. Finally, we showed no change over time in a small group of individuals with dopamine transporter single-photon emission computed tomography scans without evidence for dopamine deficiency. The nM-EDL and M-EDL components of the MDS-UPDRS provide an effective, relevant measure of change in the broad spectrum of symptoms of PD over the first decade of the disease.

Single-Photon Emission Computed Tomography Appropriateness

In this issue of Circulation , Doukky et al1 report findings from a cohort of 1511 patients from 11 outpatient community-based practices (20 primary care physicians and 2 cardiologists) in the Chicago metropolitan area. The patients underwent single-photon emission computed tomographic (SPECT) myocardial perfusion imaging and were then followed up for 27±10 months for major adverse cardiac events: death, death or myocardial infarction, and cardiac death or myocardial infarction. The SPECT studies were categorized on the basis of the 2009 appropriate use criteria (AUC) as appropriate, uncertain, or inappropriate. The investigators report that 823 patients (54.5%) underwent SPECT scans that were classified as appropriate or uncertain and 688 patients (45.5%) underwent SPECT scans that were classified as inappropriate. In those patients whose SPECT scans were appropriate or uncertain, abnormal scans were of significant value in predicting major adverse cardiac events with hazard ratios of 3.1 to 3.7 compared with normal scans. However, in those patients undergoing SPECT classified as inappropriate, abnormal SPECT scans did not achieve statistical significance in predicting major adverse cardiac events, although the hazard ratios ranged from 2.3 to 11.8. Regardless of the appropriateness of SPECT, the presence of ischemia on SPECT, reflected in the summed difference score (SDS), predicted subsequent coronary angiography and revascularization. As the investigators indicate, this is the first large study validating the prognostic implications of SPECT AUC, further supporting its clinical utility. In this editorial, we examine both the internal and external validity of this study to place it in context for evidence-based clinicians. Article see p 1634 Is the study internally valid? That is, do the data justify the conclusions? This study has a number of strengths, beginning with the size of the cohort and the several-year duration of follow-up. Although follow-up was >99% complete, a number of patients were …

Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue

Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system. In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative (99m) Tc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF. This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative (99m) Tc-sestamibi SPECT scanning.

Athletic Participation in Children with Symptomatic Spondylolysis in the New York Area

The purpose of this study was to assess athletic activities associated with spondylolysis in children and adolescents in a New York metropolitan tertiary referral center. We retrospectively evaluated 137 consecutive cases of symptomatic spondylolysis presenting to one of two pediatric orthopedic spine surgeons. Ten patients who did not participate in any organized athletics were excluded, leaving 127 children for analysis. Data regarding spondylolysis and athletic participation were gathered for analysis. One hundred and twenty-seven patients were analyzed (mean age, 13.9 ± 2.2 yr). All patients had initial x-rays, with nearly all obtaining further advanced level imaging to confirm the diagnosis of spondylolysis. Magnetic resonance imaging was obtained in 42.5% of cases, limited computed tomography scan in 29.1% of cases, and single-photon emission computed tomography scan in 23.6% of cases. The most common location of spondylolysis was at the L5 level (74%), of which 43.6% were bilateral. Of the overall cohort, 2.4% had spondylolysis at multiple levels. The most common athletic activities associated with spondylolysis in this cohort were soccer (19.3%), basketball (17.2%), and lacrosse (9.4%). Although previous reports have implicated participation in various sports in the development of symptomatic spondylolysis in children, lacrosse and baseball have rarely been associated with spondylolysis. We found that in the New York metropolitan area, soccer, basketball, lacrosse, baseball, tennis, and football were most commonly associated with spondylolysis. Therefore, we emphasize consideration of spondylolysis in these children if they present with low back pain. These results may be used to counsel parents and young athletes about the possibility of spondylolysis as an etiology of lumbar back pain and in educating coaches, teachers, school nurses, and primary care providers.

Quantitative SPECT/CT: SPECT joins PET as a quantitative imaging modality

The introduction of combined modality single photon emission computed tomography (SPECT)/CT cameras has revived interest in quantitative SPECT. Schemes to mitigate the deleterious effects of photon attenuation and scattering in SPECT imaging have been developed over the last 30 years but have been held back by lack of ready access to data concerning the density of the body and photon transport, which we see as key to producing quantitative data. With X-ray CT data now routinely available, validations of techniques to produce quantitative SPECT reconstructions have been undertaken. While still suffering from inferior spatial resolution and sensitivity compared to positron emission tomography (PET) imaging, SPECT scans nevertheless can be produced that are as quantitative as PET scans. Routine corrections are applied for photon attenuation and scattering, resolution recovery, instrumental dead time, radioactive decay and cross-calibration to produce SPECT images in units of kBq.ml(-1). Though clinical applications of quantitative SPECT imaging are lacking due to the previous non-availability of accurately calibrated SPECT reconstructions, these are beginning to emerge as the community and industry focus on producing SPECT/CT systems that are intrinsically quantitative.

Spondylolysis in the Athlete

Spondylolysis and spondylolisthesis are common causes of low back pain in athletes. Early diagnosis is crucial in the treatment of spondylolysis, as a period of rest can lead to full recovery in most patients. Radiographs can detect most lesions, but single-photon emission computed tomography scan, bone scan, computed tomography scan, and magnetic resonance imaging may be necessary in patients with normal radiograph findings or unusual presentations. There is significant variability in the literature regarding bracing, rehabilitation, surgery, and return to play. Most patients recover with nonoperative treatment, but if surgery is necessary, pars defect repair or fusion leads to good outcomes.

Submandibular (Undescended) Ectopic Parathyroid Glands: Elusive to Surgeons and Localization Studies

Objectives: High cervical parathyroid adenomas, known as undescended adenomas, occur with a frequency of less than 0.1%, but account for 7% of failed parathyroidectomies. Such cases are scarce in the otolaryngology-head and neck surgery literature. Preoperative localization of undescended adenomas using Technetium 99-c sestamibi scintigraphy (sestamibi) is difficult due to uptake and retention of sestamibi by salivary gland tissue. Methods: We present a review of the literature and two surgeons’ experience involving undescended parathyroid glands complicating the treatment of patients with primary (cases 2,3) and secondary (case 1) hyperparathyroidism. In case 1, a 52-year-old dialysis-dependent male experienced recurrent secondary hyperparathyroidism, requiring three operations over two years to excise all parathyroid glands. The right inferior gland was localized to the submandibular region prior to the final operation. In case 2, two sestamibi–single-photon emission computed tomography scans were proven incorrect when a contralateral undescended adenoma was located in a 54-year-old female at surgical exploration. In case 3, a 49-year-old male with a non-localizing scan underwent a failed neck exploration, complicated by acute pancreatitis postoperatively. The surgeon’s suspicion of an undescended adenoma was confirmed by computed tomography; the adenoma was excised. Results: When sestamibi scans are inconclusive, the contour and symmetry of uptake in and around the submandibular glands should be scrutinized. Thallium-pertechnetate subtraction scanning (TPSS) as a second line modality may be useful. Undescended glands must be considered during an unyielding, thorough parathyroid exploration. Conclusions: Surgeons should consider the possibility of undescended adenoma, and use the aforementioned localization techniques when sestamibi scans are inconclusive.

Assessment of Inter-modality Spatial Alignment Accuracy in Hybrid Single Photon Emission Computed Tomography in Patients with Hand and Wrist Pain.

Single photon emission computed tomography (SPECT) and computed tomography (CT) integrated in one system (SPECT/CT) is an effective co-registration technique that helps to localize and characterize lesions in the hand and wrist. However, patient motion may cause misalignment between the two modalities leading to potential misdiagnosis. The aim of the present study was to evaluate the hardware-based registration accuracy of multislice SPECT/CT of the hand and wrist and to determine the effect of misalignment errors on diagnostic accuracy. A total of 55 patients who had multislice SPECT/CT of the hand and wrist between July 2008 and January 2010 were included. Two reviewers independently evaluated the fused images for any misalignments with six degrees of freedom: Translation and rotation in the X, Y and Z directions. The results were tested against an automated fusion tool (Syntegra). More than half of the patients had moved during SPECT scanning (Reviewer 1: 29 patients; Reviewer 2: 30 patients) and they all originated in the Y-direction translation (vertical hand motion). Five fused images had significant misalignment errors that could have led to misdiagnosis. The Wilcoxon test indicated statistically non-significant difference (P > 0.05) between reviewers and statistically non-significant difference between the reviewers and software registration. The study also showed high inter-reviewer agreement (κ = 0.87). Hand movement during the SPECT scan was common, but significant misalignments and subsequent misdiagnosis were infrequent. Future studies should investigate the use of hand and wrist immobilization devices and reductions of scan time to minimize patient motion.

TH-A-WAB-04: Respiratory Sorted Imaging Using Region-Of-Interest Robotic Multi-Pinhole SPECT System

Purpose: Single Photon Emission Computed Tomography (SPECT) may provide important information on tumors in the thorax and abdomen. Respiratory sorted imaging using conventional full cross-section methods is generally degraded by noise. The purpose is to investigate noise reduction by region-of-interest (ROI) SPECT. Methods: The 4D XCAT phantom was computer simulated with a 10mm diameter tumor added in the right lung. Respiratory motion was simulated for 6 and 10 phases, accomplished by simulating 30 frames in one 5sec respiratory cycle. A non-sorted phantom was generated by summing the 30 phantoms to mimic motion blur. A static phantom with no respiratory motion was simulated using one of the 30 phantoms. The maximum tumor motion was 2cm Sup/Inf and 1.2cm AP. Projections were computer simulated for 4-minute scans with a reference conventional parallel-hole collimated SPECT and a 49-pinhole SPECT that was optimized to image a 7cm diameter region-of-interest(ROI) encompassing the tumor and its motion. Noisy projections were then generated with random Poisson noise. The SPECT images were reconstructed by OSEM with up to 7 iterations. Images were evaluated as a function of phase by visual inspection and root mean squared error (RMSE). Results: The tumor was visualized well above background in most phases for the 49-pinhole SPECT scan. Visual quality was not as good for the parallel-hole scan. The 49-pinhole SPECT resulted in smaller RMSEs than the broader cross-section parallel-hole detector. RMSE values were around 0.11 for the 49-pinhole SPECT scan and 0.18 for the parallel-hole SPECT scan. The RMSEs for 10 respiratory phases were similar to that of 6 phases. Conclusion: The higher sensitivity and resolution of ROI imaging can alleviate noise effects of respiratory sorted imaging, provided the motion range is within the ROI. The specific ROI SPECT system could enable this gated imaging on-board radiation therapy machines. PHS/NIH/NCI grant R21-CA156390-01A1

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.

Neuroimaging of rapid eye movement sleep behavior disorder: transcranial ultrasound, single-photon emission computed tomography, and positron emission tomography scan data

Idiopathic rapid eye movement sleep behavior disorder (iRBD), which typically develops in middle-aged individuals or later and progresses chronically, is a common clinical manifestation of Lewy body-related syndrome. It is important that combinations of neuroimaging markers in iRBD are considered for the purpose of diagnosing neurodegenerative diseases such as Parkinson disease (PD), dementia with Lewy body disease (DLB), or multiple system atrophy (MSA) at an early stage. Important advances have been made in the diagnosis of PD or DLB using imaging methods such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scans or transcranial B-mode ultrasonography (TCS). These methods are important in clinical research, in which the identification of biomarkers for iRBD offers diagnostic opportunities and points the way to new therapeutic strategies. This review focuses on neuroimaging studies of rapid eye movement sleep behavior disorder (RBD) patients using techniques such as TCS, SPECT, and PET scans.

Effect of a Nicotine Vaccine on Nicotine Binding to β2*-Nicotinic Acetylcholine Receptors In Vivo in Human Tobacco Smokers

Nicotine promotes smoking partly by binding to β2-containing nicotinic acetylcholine receptors (β2*-nAChRs) in the brain. Smoking one tobacco cigarette results in occupation of 80% of β2*-nAChRs for more than 6 hours. This likely contributes to maintenance of smoking dependence and cessation difficulty. Developing nicotine vaccines could improve treatments. The authors used [123I]5-I-A-85380 single photon emission computed tomography (SPECT) to evaluate the effect of 3'-AmNic-rEPA on the amount of nicotine that binds to β2*-nAChRs in smokers' brain cortical and subcortical regions. Eleven smokers who smoked an average of 19 cigarettes per day, had smoked for 10 years on average, and met criteria for nicotine dependence were given SPECT scans on two days: before and after immunization with 4-400 μg of 3'-AmNic-rEPA. On scan days, three 30-minute baseline emission scans were followed by intravenous administration of nicotine (1.5 mg/70 kg body weight) and up to nine 30-minute emission scans. β2*-nAChR availability was quantified as VT/fP (total distribution volume divided by free plasma concentration), and nicotine binding was derived by the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding. Nicotine bound to β2*-nAChRs correlated positively with nicotine injected before but not after vaccination. The daily number of cigarettes and desire for a cigarette decreased after vaccination. This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between administered nicotine and nicotine available to occupy β2*-nAChRs.