Iranian Journal of Nuclear Medicine
Volume:31 Issue: 2, Summer-Autumn 2023

The purpose of this study was to evaluate possible preventive role of quercetin on doxorubicin (DOX) induced kidney toxicity using Tc-99m Dimercaptosuccinic Acid ([99mTc]Tc-DMSA) renal cortical scintigraphy and biochemical approaches. 28 Male Wistar rats were separated into four groups. First group was intraperitoneally (i.p.) injected saline and regarded as the control group; second one was received 18 mg/kg/i.p doxorubicin for three days at a 24 h interval; the third and last group received 10 mg/kg and  100 mg/kg quercetin for 21 days and for the last 3 days doxorubicin and quercetin were administrated together at the same time. On the 22 th day of the experiment, [99mTc]Tc-DMSA renal cortikal scintigraphy and biochemical parameters were measured.DOX administration significantly increased blood urea nitrogen (845%) and creatinine (702%) levels in serum; nitric oxide (158%), plasma tumor necrosis factor-alpha (233%) and interleukin-6 (191%) levels in kidney tissue, and also reduced [99mTc]Tc-DMSA uptake by 29% in the kidneys as well. Pre-treatment with quercetin mitigated such alterations in all mentioned parameters. All data indicate that oxidative stress and inflammatory processes are involved in DOX-induced nephrotoxicity, which might be decreased by quercetin.In addition, [99mTc]Tc-DMSA scintigraphic may be a good method for demonstrating doxorobucin-induced renal injury.

Quantitative accuracy in SPECT is mainly affected by collimator penetration and scattering, particularly for high-energy imaging. Lofthole collimation offers superior performance in terms of penetration and scattering. In this research, the GATE Monte Carlo simulator was exploited to calculate edge penetration and scattering in the lofthole collimator using an in-air and in-phantom point source of Tc-99m and I-123. The performance of the lofthole was then compared to that of a pinhole. Both lofthole and pinhole collimators were assumed to have the same geometry including an aperture diameter of 3.04 mm and an opening angle of 75°. Furthermore, the angular distribution of the scattering and penetration were investigated for a multi-lofthole collimator. The results show that penetration, scattering, and sensitivity are all a function of the photon energy. The penetration and scattering of the pinhole are about 4% higher than that of the lofthole collimator, for Tc-99m SPECT. Compared to the Tc-99m, I-123 SPECT suffers from approximately 1.5- and 1.42-fold higher penetration and scatter fractions, respectively, for lofthole aperture. Moreover, the lofthole collimator presents a higher sensitivity compared with the pinhole (0.030 versus 0.023 for the Tc-99m SPECT). In addition, the findings exhibit a reduction in sensitivity by increasing the photon incidence angle. Both scattering and penetration fractions illustrate a decreasing trend across the angle of incidence. Compared to pinhole, the lofthole offers superior performance in terms of scattering and penetration for both low- and high-energy SPECT imaging.

Correlation of Glomerular Filtration rate (GFR) obtained by Double Plasma sampling method (DPSM), Single Plasma sampling method (SPSM), Cockcroft Gault method and Gates’ method in prospective voluntary kidney donors. Fifty-six prospective donors sent for [99mTc]Tc-DTPA renogram were prospectively included. GFR was obtained by Double Plasma sampling, Single Plasma sampling, Cockcroft Gault and Gates’ method using standard protocols. Intra-class ccorrelation coefficient, Pearson correlation coefficient and difference in mean and median GFR between GFR values obtained by DPSM as reference method and other methods were calculated. GFR obtained by SPSM, Cockcroft Gault method and Gates’ method show poor, moderate and good agreement respectively with GFR obtained by DPSM (reference method). There was statistically significant mild positive correlation between GFR obtained by DPSM with GFR obtained by SPSM and statistically significant moderate positive correlation between GFR obtained by DPSM with Cockcroft Gault method and Gates’ method. The mean and median score of GFR obtained by SPSM, Gates’ method and Cockcroft Gault method were lower, higher and significantly higher respectively than GFR obtained by DPSM. GFR obtained by Gates’ method correlates well with Dual Plasma Sampling Method (DPSM, reference standard) and Cockcroft Gault Method overestimates GFR by a large extent amongst prospective voluntary kidney donors.

The aim of this study was to develop an optimized formulation for labeling a third-generation bisphosphonate, zoledronic acid with [99mTc] Tc to achieve the best formulation in preparing an ideal skeletal radiotracer.  Radio-complex yield and purity, stability, biodistribution and imaging in normal rat were investigated.  

The samples containing different amounts of zoledronic acid, ascorbic acid and stannous chloride were prepared and labeled with [99mTc]technetium pertechnetate. TLC methods were used to determine the radiochemical purity. The stability was determined in saline and human serum solutions. Lipophilicity was calculated by measuring radio-complex that was divided between organic and aqueous phases. In vitro bone affinity was studied through hydroxyapatite binding assays. Considering the decomposition of radioactivity, biodistribution of radio-complex was assessed based on the percentage of injected activity per gram of organ (% IA/g).

[99mTc]Tc-zoledronic acid was prepared easily with high yield while 100 µg, 0.34 µmol of zoledronic acid as a ligand and 100 µg, 0.44 µmol SnCl2 as a reducing agent were used. Radiochemical purity of radio-complex was more than 99% with specific activity of 8050 MBq/µmol. The radio-complex showed rapid blood washout along with high bone uptake value (4.53 ± 0.14 % IA/g at 2 h post injection).

Under optimized condition, [99mTc]Tc-zoledronic acid was prepared with high purity and stability together with high bone affinity and rapid blood clearance, make this radio-complex an ideal agent with great potential for skeletal imaging.

Excessive expression of the αvβ3 integrin receptors is seen in rapidly multiplying endothelial cells, including cancerous growth of various tumors. αvβ3 integrin receptors’ specific targeting by peptides containing the RGD motif makes these short sequences a suitable nominee for diagnostic imaging and lung cancer follow-up. A high-affinity RGD-containing peptide is designed. The di-RGD peptide has a greater affinity along with tumor-selective targeting properties. Peptide labeling with gadolinium for magnetic resonance imaging was accomplished, permitting efficient cancer molecular imaging accompanied by high spatial resolution. This peptide will have better sensitivity for the early identification of tumors and is appropriate for follow-up routines. DOTA-E(cRGDfK)2 was labeled with Gd(ΙΙΙ) effectively. The cytotoxicity to cells was measured. The biodistribution was evaluated in a mouse model for lung cancer. The very early diagnostic capacity of the Gd-RGD peptide was studied using MR molecular imaging. MR imaging shows high binding specificity of Gd(ΙΙΙ)-DOTA-E(cRGDfK)2 to A549 lung tumor in mice. Gd-DOTA-E(cRGDfK)2 did not show cytotoxicity at high concentrations and on different cell lines. Biodistribution studies confirm tumor uptake up to 24h after the injection. The peptide-based contrast agent leaded to an improved tumor contrast enhancement at a dose of 0.1 mmol Gd/kg. The tumor uptake peaks were after 30 min of injection. A clear picture of the tumor was seen in all images. Gd(ΙΙΙ)-DOTA-E(cRGDfK)2 can be used as a peptidic MR imaging contrast agent enabling initial detection of different cancers overexpressing the αvβ3 integrin receptors and can be a prospective candidate in clinical studies of non-small cell lung carcinoma.

Gated myocardial perfusion SPECT (GMPS) using [99mTc]Tc-MIBI allows the cardiac function assessment in addition to the myocardial perfusion. Although the prone position has been suggested as a complementary protocol in GMPS, there is no firm recommendation on its effect on function and physiologic conditions of cardiac. We aimed to evaluate the impact of supine and prone positions on left ventricular end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (LVEF), and heart rate (HR). Ninety-six patients with no history of ischemic heart disease or cardiomyopathy participated in this study. Using GMPS at both supine and prone positions, volume-based cardiac function was evaluated. ESV, EDV, LVEF, and HR were obtained and compared between supine and prone positions. A two-tailed p-value of < 0.05 was considered significant. Using GMPS, no significant difference in ESV, EDV, LVEF, and HR was demonstrated between the two positions (p-value>0.05). The mean LVEF results derived from the supine versus prone position were 67.22% (42–93%) vs. 64.22% (41–89%) (p-value=0.71). ESV results were 23.28 vs. 27.23 (p-value=0.39). EDV results were 65.78 vs. 70.33 (p-value=0.27). Furthermore, HR results were close to each other in supine 72.22 (45-106) and prone 74.99 (47-110) positions (p-value=0.68). It seems that prone positioning causes no considerable change in cardiac volumes. As a result, the prone position can be an acceptable alternative to the supine position when volume-based assessments are considered.

Peptide-based radiopharmaceuticals have great advantages that make them one of the most interesting radiotracers for theranostic applications. This study aims to develop [64Cu]Cu-DOTATATE as a beneficial agent for PET imaging of neuroendocrine tumors (NETs). 64Cu was produced via 68Zn(p,αn)64Cu reaction using 30 MeV Cyclotron. [64Cu]Cu-DOTATATE was prepared at optimized labeling conditions by varying parameters. The radiochemical purity of [64Cu]Cu-DOTATATE was checked by various methods. The stability of the final radiolabeled compound was assessed in PBS buffer and human serum. Binding affinity and internalization rate of [64Cu]Cu-DOTATATE were studied on the Rat C6 glioma cell line.  The biodistribution of [64Cu]Cu-DOTATATE was studied in normal and tumor-bearing rats at different intervals. Finally, the images were taken after the administration of the radiopharmaceutical by a dual-head SPECT system. [64Cu]Cu-DOTATATE was produced with radiochemical purity >99% (RTLC & HPLC) and specific activity of 22.4 GBq/mg in optimized conditions. [64Cu]Cu-DOTATATE demonstrated high stability in vitro and in vivo. The binding studies showed a high binding affinity of the radiopharmaceutical to somatostatin-receptor-expressing cells. The internalization studies showed >58% of the radiopharmaceutical is internalized into the C6 cells within 6 h after incubation. The biodistribution of [64Cu]Cu-DOTATATE in normal and tumor-bearing rats showed high uptake of somatostatin-receptor-expressing organs and tumors, respectively. The images of tumor-bearing rats were consistent with the results of the biodistribution study. Preclinical studies of [64Cu]Cu-DOTATATE showed that the radiopharmaceutical has a high potential for domestic use in  PET imaging of patients with NETs.

Previous studies suggested the prognostic significance of the number of involvement sites in 2-[18F]FDG PET/CT imaging in multiple myeloma. The aim of this study was to evaluate the significance of the findings that might be observed in case of whole body (extended field) imaging in the 2-[18F]FDG PET/CT in multiple myeloma patients. The imaging findings of 70 patients (33 female, 37 male; mean 66.3±10.2 years old) with the diagnosis of multiple myeloma 2-[18F]FDG PET/CT were evaluated retrospectively. The patients were divided into two groups; Group 1; the patients with pathologic findings (lytic lesions with maximum standardized uptake value of >4) in extended field imaging and Group 2; the others respectively. The comparison of the two groups revealed no statistical significant difference between their index lesions uptake values (P>0.01). The time to progression of the groups were not significantly different (p=0.08) in the mean 27.2±32.5 months follow up. However, the ratio of disease specific mortality was higher (33% vs 5%) in the group of patients with extended field imaging findings. Extended field imaging might point out higher disease specific mortality but this issue has to be evaluated by further studies in larger series.

 Heart failure is an important life-threatening problem, with left ventricular diastolic dysfunction as a major initial pathophysiologic process and identification and treatment of related risk factors lead to better prognosis. Gated single-photon emission computed tomography (G-SPECT) myocardial perfusion imaging (MPI) is a feasible tool to evaluate the diastolic function. The aim of this study was to assess the correlation of cardiovascular risk factors with the diastolic function parameters in G-SPECT MPI. This is a cross-sectional retrospective study including 274 patients with normal ejection fraction (EF) and no previous history of heart disease. Demographic data and history of cardiovascular risk factors were collected. Correlation of quantitative functional parameters of G-SPECT including diastolic indices (peak filling rate (PFR), time to peak filling rate (TTPF), mean filling rate at the first third of diastolic phase (MFR/3), and second peak filling rate (PFR2)) with cardiovascular factors was studied using SPSS software. In this study, 274 patients with a mean age of 56 years (with 172 females) were evaluated. There was a significant relationship between age and all diastolic parameters. Diabetic patients had a significantly lower TTPF, and hypertensive patients revealed a significantly lower MFR/3. Hyperlipidemia and chronic kidney disease were not associated with any diastolic parameters. PFR was significantly lower in smokers, and family history had a significant relationship with PFR2. Most of CAD risk factors, except for CKD and hyperlipidemia, had a significant relationship with at least one parameter of the left ventricular diastolic function in G-SPECT MPI.

[68Ga]Ga-PSMA-11 PET/CT scan is an important whole-body imaging tool in oncology and is specifically used for staging and re-staging of prostate cancer, in recent years. Findings of significant focal accumulation of PSMA in the lung parenchyma without corresponding CT abnormalities are challenging and may be a cause for false positive interpretation of metastasis, caused by pulmonary microembolism due to hot-clot artifacts, as previously described in 2-[18F]FDG PET/CT studies. Here we present an unusual case of focal PSMA uptake in lung parenchyma without structural lesions on CT scan, which we believe is due to hot clot because of faulty injection techniques.

A 43-year-old female known case of Systemic Lupus Erythematous was presented with chief complaints of pain and morning stiffness in her joints since 3 months ago. Her pain was intensified after Covid-19 pneumonia. She was referred to our nuclear medicine center to rule out active arthritis with three-phase bone scan. An interesting finding was abnormal large tracer accumulation in the pelvis, which was proved to be due to myoma.

Сardiac implantable electronic device infection (CIED) is a rare complication, ranging from 0.5-1% in the first 6-12 months after device implantation. In the absence of a standardised protocol, the diagnosis of CIED infection is difficult due to a nonspecific clinical presentation. In some cases, the inflammatory process can mimicking as another cardiovascular disorder, including acute myocardial infarction. Today, the diagnosis of infection is based on the Duke criteria, including clinical, microbiological and echocardiographic data. However, the diagnostic accuracy of the criteria for device-related infective endocarditis is significantly reduced. Presented clinical case highlights the importance of increased vigilance in patients who have undergone device implantation and, in particular, device replacement, and the usefulness of nuclear imaging techniques in asymptomatic patients or patients with an atypical clinical picture.

Thyroid nodule is the most common presentation of thyroid carcinoma. Considering the indolent course of the disease, indeed, the papillary thyroid cancer (PTC) microcarcinoma puts much debate regarding large-scale cohorts on patient follow-up over several decades to detect differences in aggressiveness and outcome [1]. Lymph node metastases might be the salient manifestation of the disease. The nodal metastases usually appear in the central and to a lesser degree in the lateral neck mostly as a solid nodule and rarely in form of a cystic mass. In this study, we describe a case of lymph node metastasis from thyroid papillary carcinoma that clinically and radiologically mimicked a carotid body tumor and despite all pre-surgical evaluations; papillary thyroid carcinoma was detected in the final histopathology report. We intend to describe the initial clinical evaluation, radiological survey and pathology report.