Iranian Journal of Nuclear Medicine
Volume:16 Issue: 1, Winter-Spring 2008

In this paper, we review novel techniques in the emerging field of spatiotemporal 4D PET imaging. We will discuss existing limitations in conventional dynamic PET imaging which involves independent reconstruction of dynamic PET datasets. Various approaches that seek to attempt some or all of these limitations are reviewed in this work, including techniques that utilize iterative temporal smoothing, advanced temporal basis functions, principal components transformation of the dynamic data, wavelet-based techniques as well as direct kinetic parameter estimation methods. Extension of 4D PET to 5D PET in which the additional dimension of (respiratory or cardiac) gating is considered has also been discussed.

Although left ventricular(LV) function parameters measured by gated myocardial perfusion SPECT (GSPECT) have been validated, experimental data have revealed that the calculated the LV function parameters using GSPECT are affected by patient populations as well as particular acquisition and processing conditions. We tried to determine the normal values of GSPECT in an Iranian population. We studied 3500 Iranian patients who underwent GSPECT in an outpatient setting. To develop normal limits of LV functional indices using GSPECT, 148 patients with a low (<5%) likelihood of coronary disease and normal tomograms were selected. No one of 148 patients had known coronary artery disease, typical angina, history of hypertension, diabetes mellitus, and smoking, any abnormality in echocardiography or hyperlipidemia. They were not taking any medication known to affect LV function at least 2 days before the study. End diastolic volume (EDV), end systolic volume (ESV) and LV ejection fraction (LVEF) were calculated in rest GSPECT using iterative reconstruction and QGS (quantitative gated SPECT) software. Mean EDV, ESV and LVEF were 53.8±20.2, 14.3±10.8 and 75.0%±9.6% respectively. These data showed a Gaussian distribution, so mean±2SD would show the upper or lower limits of normal for LV functional parameters. There were the marked sex differences in mean LVVs and LVEF measurements. BMI index had not effect on the measurement of the LV functional parameters. We noticed that 85.4% of our subjects had ESV<25 ml while most of them were women (112/123, 91%). From a clinical viewpoint, each institute should use a standard protocol for the specific patient population and for the mode of SPECT acquisition and reconstruction. Normal thresholds using GSPECT, OSEM reconstruction and QGS algorithm in men and women were EDV>130, ESV>55 & LVEF<52% and EDV>77, ESV> 26 and LVEF<62% respectively.

Over expression of selected peptide receptors in human tumors has been shown to represent clinically relevant targets for cancer diagnosis and therapy. The aim of this work was to investigate Neuropeptide Y (NPY) as a new radiopharmaceutical for diagnosis of breast cancer. A neuropeptide Y analogues with Y1 receptor preference and agonistic properties was synthesized by solid phase method. After conjugation with diethylenetriaminepentaacetic acid (DTPA) labeling with 111In was performed. For labeled peptide, yield of labeling, stability in human serum, receptor binding in cell surface with internalization in SK-N-MC cells, and biodistribution in normal rat were determined. Peptide was synthesized and labeled with more than 95% purity. Radiolabeled peptide was stable in human serum and specifically binds and internalized in the cells with Y1 receptor (4h = 22%). A rapid clearance from blood pool and urinary with hepatobiliary excretion were observed. Our results showed that this peptide can be considered as a candidate for diagnosis of breast tumors.

Ubiquicidin 29-41 (UBI) is a fragment of the cationic antimicrobial peptide that is present in various species including humans. The purpose of this study was to investigate radiochemical and biological characteristics of [6-hydrazinopyridine-3-carboxylic acid (HYNIC)]-UBI 29-41 designed for the labeling with 99mTc using tricine as coligand. Synthesis was preformed on a solid phase using a standard Fmoc strategy and HYNIC precursor coupled at the N-terminus. Purified peptide conjugate was labeled with 99mTc at 100°C for 10 min. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate stability and affinity to human serum was challenged for 24 hours and its in vitro binding to bacteria was assessed. Biodistribution and accumulation of radiopeptide in staphylococcus aureus infected mice were studied using scintigraphy and ex vivo counting. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. The stability of radiolabeled peptide in human serum was excellent. In vitro studies showed 70% of radioactivity was bound to bacteria. After injection into mice with a bacterial infection, removing from the circulation occurred mainly by renal clearance and site of infection was rapidly detected within 30 min. Target to nontarget muscle ratio was 2.099 ± 0.05% at 30 min post injection. [99mTc-HYNIC]-UBI 29-41 showed favorable radiochemical and biological characteristics which permitted detection of the infection with optimal visualization within 30 min.

Ordered subset expectation maximization (OSEM), is an effective iterative method for SPECT image reconstruction. The aim of this study is the evaluation of the role of system matrix in OSEM image reconstruction method using four different physical beam radiation models with three detection configurations. SPECT was done with an arc of 180 degree in 32 projections after injection of 2 mCi of 99mTc-pertechnetate in a heart phantom by a Siemens E.Cam gamma camera equipped with LEHR collimator and data were transferred to a PC computer for reconstruction of the images with Mathlab software. The system or probability matrixes were firstly calculated using radiation fraction of pixels for three different detection models with linear, rectangular and divergent FOV, and reduction coefficient of photons from pixels to detectors in four different radiation models of distance independent (DID), inverse distance dependence (IDD) [1/R], inverse square distance dependence (ISDD),[1/R2] and inverse exponential distance dependence(IEDD),[exp-R]. In these calculations the detector was assumed at a distance of 842 mm from the phantom center and pixel size was 6.638 mm. The divergent angle in divergent field of view was 2.08 degree. 12 Images of the phantom were reconstructed using system matrixes of 4 different radiation and 3 detection models. Qualities of the images were compared using universal image quality index, UIQI. The results shows negligible although statistically significant difference between contrast and brightness of the images, but it is possible in the organs with constant absorption coefficients such as brain, to use the system matrix with mathematical IEDD radiation model for attenuation correction in SPECT images. It is shown that variation in distance weighting factors in mathematical IEDD radiation model changes the system matrix so that the weights of deeper data decrease in image reconstruction process. Therefore, by this method contrast of the image at different depth can be controlled. Applying different beam radiation models and detection configurations in system matrix has no significant improvements on the image quality. However image contrast at different depth can be controlled by using system matrix derived from different distance weighting factor in mathematical IEDD radiation model.

Radioimmunotherapy (RIT) is a very promising new therapy for the treatment of recurrent B-Cell non-Hodgkin’s lymphoma (NHL). Iodine-131 is the most frequently used nuclide in clinical RIT, but its usefulness has been limited by dehalogenation of monoclonal antibodies labeled via conventional methods. To circumvent this problem, we have synthesized a tri-peptide consisting of non-metabolizable D amino acids attached to N-Hydroxysuccinimide (NHS). Tri-peptide was synthesized by standard Fmoc solid phase synthesis on tritylchloride resin. Labeling of tri-peptide was performed using the chloramine-T method and the conventional extraction. Radioiodination of tri-peptide was followed by conjugation to anti-CD20 antibody. In vitro stability of labeled antibody in serum and phosphate buffered saline (PBS) was measured for 48hr by (thin layer chromatography) TLC. Raji cell line was used to test cell binding of the labeled anti-CD20. The chemical purity of synthesized peptide as assessed by analytical (high performance liquid chromatography) HPLC was 95%. Labeling of tri-peptide resulted in a radiochemical yield of 50-71% with radiochemical purity of > 95%. At Rituximab concentration of 10mg/ml, coupling efficiencies of 65-80% was obtained with radiochemical purity of 95% and Specific activity (SA) of 185MBq/mg (5mCi/mg). This study showed that labeling monoclonal antibodies with radioiodine by non-metabolizable D amino acids will improve bio-stability of the product.

Studies with single photon emission computed tomography (SPECT) have revealed inconsistent changes of regional cerebral blood flow (rCBF) in schizophrenia. Some studies investigated the rCBF and its relationship with psychopathology, positive and negative symptoms in treated patients. However, there is a little information about the pattern of rCBF in recently untreated or never treated schizophrenic patients. The aim of this study was to evaluate the pattern of rCBF of the drug-naïve or drug free schizophrenic patients. Thirty-three patients with schizophrenia participated in the study. For each subject, the regional brain perfusion was evaluated with SPECT and the clinical state was assessed according to PANSS and CGI in a medication-free state. Also a group of 12 cases without any history of neurological or psychological disorder was enrolled as a control group for comparing of the SPECT data. Regional perfusion indices (RPI) were defined as mean count per pixel in each of 25 brain regions normalized to the mean count per pixel of the whole brain. The RPI patterns were compared in control and patient subjects. In comparison with control subjects, the RPI of the anterior cingulate and inferior parts of the prefrontal and temporal cortices of the schizophrenic patients are significantly higher while the RPI of the occipital and parietal regions are unilaterally lower. Different schizophrenic patients showed hyperperfusion as well as normal or hypoperfusion in different regions of the brain cortex. However, hyperperfusion rather than hypoperfusion mainly is seen in the inferior prefrontal and temporal regions, while hypoperfusion patterns are more prominent in the cerebellar, occipital, parietal and dorsolateral prefrontal cortices. Different patterns of brain perfusion are seen in drug-free or drug-naïve patients with schizophrenia. Hyperperfusion in the frontal and temporal regions and hypoperfusion in the cerebellar, parietal and dorsolateral prefrontal cortices are the most predominant abnormal patterns in these cases.

We present a female patient with atypical chest pain who was referred to our department for ischemia evaluation. 99mTc-MIBI myocardial perfusion scan with dipyridamole stress was performed. Sub-diaphragmatic activity in the hepatic tissue and then in the bowel loops caused severe overlap on the inferior wall even on consecutive delayed images. Dipyridamole stress was repeated for the patient with 201Tl. The study was interpretable this time without any interfering sub-diaphragmatic activity.