Iranian Journal of Nuclear Medicine
Volume:31 Issue: 1, Winter-Spring 2023

This study evaluates scan time reduction using time-of-flight (TOF) PET, when quantitative parameters including volumetric measures are considered.

32 patients were included in the study. The reconstruction parameters for TOF were 2 iterations, 18 and 24 subsets, and for non-TOF was 3 iterations and 18 subsets. A post smoothing filter with FWHM of 5.4 mm and 6.4 mm were used for TOF and 6.4 mm for non-TOF. TOF reconstruction was performed with 2, 2.5 and 3 min/bed position, and 3 min/bed position scan time was applied in non-TOF. Quantitative parameters such as coefficient of variation (COV), signal-to-noise ratio (SNR), lesion-to-background ratio (LBR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were utilized. Standard uptake value (SUV) was also measured. Different segmentation thresholds were studied.

Improvement in SNR for TOF relative to non-TOF was observed when utilizing 18 subsets, 5.4 mm filter size with 3 min scan time/bed position (P-value<0.0001), and for 18 subsets, 6.4 mm filter size when 2.5- and 3-min scan time/bed positions was applied (P-value≤0.02). Scan time reduction did not illustrate significant variation for the SUVs and lesion size. In all TOF protocols for both TLG and MTV, the measured values decreased with increasing segmentation thresholds, as expected, with significantly more impact for higher thresholds (70%, 75%). Meanwhile, higher values were observed for higher post smoothing filter in each specified threshold. With increasing of the threshold, ΔTLG was increased with more impact for higher post smoothing filter. ΔMTV were -10.10±11.09 (-1.35±8.59) and 0.68±17.51 (12.42±18.90) in 2 min/bed position with 5.4 (6.4 mm post smoothing filter) for threshold of 45% and 75% respectively.

Scan time reduction from 3 to 2 min can be obtained with TOF in comparison with non-TOF, especially when higher segmentation threshold values with higher subset number (24) and 6.4 mm filters are utilized.

Large Vessel Vasculitis (LVV) is a chronic inflammatory process that affects the aorta and its main branches. LVV include Takayasu’s Arteritis (TA) and Giant Cell Arteritis (GCA). The diagnosis of TA is made according to clinical criteria and based on the criteria of the American College of Rheumatology (ACR). Monitoring of disease progression and response to treatment is also done using the National Institutes of Health (NIH) criteria. Despite these criteria, diagnosing and evaluating TA activity is a challenging issue and usually occurs in the advanced stages of the disease. The lack of a comprehensive and non-invasive diagnostic method for diagnosing and monitoring the course of TA is obvious. The aim of this study was to evaluate the diagnostic agreement between 2-[18F]FDG PET-CT scan and clinical criteria for assessing TA disease activity. 

Twenty-four known cases of TA, who met the inclusion criteria, were enrolled in this study. The disease-related constitutional signs and symptoms, as well as laboratory and imaging findings were recorded. Patients underwent 2-[18F]FDG PET-CT imaging with standard protocol. Fused PET-CT images were reviewed and, if necessary, images without attenuation correction were visualized as well. Also, 24 control patients of the same age and sex, among the patients who were referred to the imaging center for oncological indications were examined to compare the uptake of different vascular territories.

Out of 15 active patients (according to the NIH criteria), 2-[18F]FDG PET-CT scan was able to correctly identify 14 patients. Also, out of 9 inactive patients, PET scan was negative in eight patients showing that 2-[18F]FDG PET-CT scan could well differentiate between active and inactive status of the disease (p-value < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of scan in this study were 93.3%, 88.9%, 93.3% and 88.9%, respectively. The study also showed that the severity of vascular lesion uptake was not affected by immunosuppressive drugs, including corticosteroids and methotrexate. Scan findings were comparable with the results of anatomical imaging in terms of disease activity and the number of vascular lesions with p-value = 0.1 and 0.304, respectively.

In this study we showed that 2-[18F]FDG PET-CT has comparable results with other imaging modalities and NIH criteria; therefore, it can play an important role in assessing the severity of TA, even when patients are on immunosuppressive drugs.

 Particular characteristics of 89Zr to produce various labeled compounds are crucial for developing radioimmunopharmaceuticals for clinical trials. This study aimed to produce 89Zr for radiolabeling purposes as radioimmunoPET grade precursor.

 The computational calculations for 89Zr production via 89Y(p,n)89Zr reaction were performed using TALYS-1.8 and ALICE-91. 89Zr was produced by the proton bombardment of the yttrium pellet using a 30 MeV cyclotron. ZR resin was used for the separation of 89Zr from the target. The radionuclidic purity was assessed by a high purity germanium detector. The inductively coupled plasma spectrometry and instant thin layer chromatography methods were considered for chemical and radiochemical purity assessments, respectively. The biodistribution of [89Zr]Zr-oxalate was studied in Wistar rats by both sacrification and imaging. [89Zr]Zr-DFO-trastuzumab was produced as a proof of concept for a radioimmunoPET labeling.

 Considering the cross-section of 89Y(p,n)89Zr reaction, 14 MeV proton energy was selected for 89Zr production, while the yttrium pellet target was irradiated at least for 125 µAh,. 89Zr was finally prepared with a yield of 25.9±1.48 MBq/µAh, a specific activity of 344.1 MBq/µg, the radionuclidic and radiochemical purity higher than 99.99% and 99%, respectively. Total amount of the metal ions in the final solution was less than 0.1 ppm. Biodistribution of [89Zr]Zr-oxalate demonstrated high accumulation in the bone, lungs, and heart. [89Zr]Zr-DFO-trastuzumab was produced with a radiochemical purity higher than 99% and specific activity of 74 GBq/g in about 2 hours.

 [89Zr]Zr-oxalate was produced with suitable activity and high purity for the preparation of the radioimmunopharmaceuticals.

 Normal population data is necessary for the quantification of myocardial perfusion studies (MPS). In Iran, data embedded in the Cedars Cardiac Suite, from young Californian volunteers, is used. We generated an Iranian female dataset and compared it with the original one.  

 Thirty-one females aged 20-45 years without coronary artery disease risks were recruited. They underwent two-day exercise stress (Bruce protocol) and rest gated SPECT MPS. [99mTc]Tc-MIBI was injected (15 mCi) and imaging for stress and rest phases were started 60 and 90 min later, respectively, in supine and prone positions. A dual head gamma camera was used, ProSPECT (PNP, Tehran, Iran). Polar plots were extracted and a normal database generated.

 Visually, none of the participants presented a reversible perfusion defect. Index for transient ischemic dilation was 1.1±0.15 and 1.1±0.14, respectively for prone and supine positions; lung heart uptake ratio 0.3±0.1 and 0.28±0.1; ejection fraction 69.8±7.8 and 70±8; peak filling rate 2.9±0.75 and 2.9±0.95 end-diastolic volume/sec; and time to peak filling rate at 178±44.5 and 203±49.5 millisecond. Compared to the original prone Californian normal database, total perfusion defect for stress and rest was 12.1±6.7 and 5.3±5.2, and for the supine position 10.1±0.5.4 and 4.0±3.4, respectively.

 Iranian normal database for MPS was generated with a remarkable difference from the original normal data.

 Metalloporphyrin-based contrast agents can improve probe functionality such as biocompatibility, prolonging presence in blood, and specific tumor accumulation. Herein, we report synthesis, structural characteristics, quality control, and nuclear imaging of new metalloporphyrin-based contrast agents.

 To combine photodynamic therapy (PDT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computerized tomography (SPECT), Gadolinium-proto porphyrin IX complex was synthesized via direct complexation method, then the metalloporphyrin (MP) was labeled with gallium-67 and gallium-68 in separated runs. In-vivo biodistribution studies were performed in mice bearing breast tumor (4T1 mouse mammary tumor cell line) and normal rats (for better visualization).

 Adsorption of the labeled compound into the tumor (ID/g % up to 4.6%), despite the small size of the tumor, had an upward trend at all times, and high and fast (less than 45 min) uptake of radiotracer in cancerous tumors was observed.  

  Fast and high tumor uptake revealed that this radiotracer could potentially be used as a theranostic agent.

Effective management of radioiodine (RAI)-refractory differentiated thyroid cancer is a challenge due to limited treatment options. Multikinase inhibitor therapy including sorafenib has been an optional treatment in recent years. This study aims to compare the clinical benefit rate, progression free survival, and quality of life between patients who received limited dose of sorafenib (200-400 mg per day) as opposed to the control group.

Twenty-two patients who received sorafenib and twenty-three cases in the control group were studied for two years. Baseline variables were comparable between two subgroups. The results of diagnostic imaging methods were also taken into consideration. Quality of life was measured using the EORTC (European Organization for Research and Treatment of Cancer) quality of life questionnaire.

Based on the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, clinical benefit rate was 77.3% and 47.8% in sorafenib and control subgroups respectively (p value=0.042). The median of progression free survival for the sorafenib subgroup was 24 months and in the control subgroup was 22 months (p value=0.020). In a comparison between two groups regarding their quality of life, all subscales were statistically insignificant between the two groups except for the symptom subscale (p value=0.001).

Low-dose sorafenib maintenance therapy is an effective treatment option in RAI- refractory differentiated thyroid cancer with the main effect of stabilizing the disease. Except for unpleasant but tolerable adverse effects, this treatment has no significant negative influence on the quality of life as far as the physical, role, cognitive, emotional, financial and social functions are concerned.

The present study aims to assess pre-thyroidectomy thyroid hormone disturbances among patients suffering from differentiated thyroid carcinoma (DTC).

This retrospective study was performed from September 2020 to March 2021. We analyzed the hospital files of 710 patients with DTC who underwent thyroidectomy and referred to nuclear medicine department from April 2013 to September 2019. Demographics, TNM stage, pre-surgery thyroid function tests, time-interval to achieve a complete response, recurrence rate, one-year response, final response, and the need for alternative treatment modalities were extracted. Then, we analyzed the potential association of pre-surgery TSH levels with the initial disease stage and treatment response. Chi-Square, Analysis-of-variance, and Kruskal-Wallis tests were used where appropriate.

The mean age of participants was 40.39 ± 13.85 years. History of Hashimoto's disease was detected in 130 (18.3%) patients. Multi-focal DTC was found in 221 (31.2%) patients. Lymph node involvement was significantly higher among men (p = 0.001). Men also had significantly higher thyroglobulin levels (p = 0.025). No statistically significant association was found between pre-surgery thyroid function status and TNM stage or multifocality of the malignancy. Baseline thyroid function tests also did not show a statistically significant relationship with thyroglobulin, anti-thyroglobulin antibody, time to first excellent response, and follow-up duration.

Baseline thyroid function status may not change the outcome of DTC. It could also be plausible that thyroid dysfunction before surgery would not increase invasiveness nor impact the treatment-response of the tumor compared to euthyroid patients.

 For the interpretation of myocardial perfusion imaging, considering non-perfusion variables, such as transient ischemic dilatation (TID), are also important in diagnostic and prognostic evaluation of a patient. TID has a relatively high false positive and false negative results, which reduces its diagnostic and prognostic values. In this study, we aimed to compare the accuracy of TID after normalization based on changes in LV wall mass.

 Patients referred for dipyridamole myocardial perfusion imaging single-photon emission computed tomography (MPI/SPECT), one to two year prior to the study with TID ratio >1 were enrolled. Patients with any previous history of revascularization and structural heart disease were excluded. Follow-up was done by phone call. The occurrence of cardiac death, myocardial infarction, revascularization or evidence of abnormal angiography during one year after MPI was considered positive for short-term cardiac events. The corrected TID (cTID) was calculated by the following formula: cTID = TID/(Wallstress/Wallrest).

 Among 196 participants, 30 (15%) had cardiovascular events during the follow-up. The area under the receiver operating characteristic (ROC) curve for the short-term prognosis of the cardiac events were 0.57 and 0.50 for cTID and TID with a p-value of 0.17 and 0.92, respectively. Considering the best cut-off points that were achieved by ROC curves, cTID showed significant odds ratio (OR: 2.53) for prediction of short-term cardiac events, while respecting, TID failed to be statistically significant.

 Making correction on TID using LV wall volumes can improve short-term prognostic value of this variable.

 Recently, [68Ga]Gallium lyophilized kit has been widely practiced as it simplifies the radiolabeling process. Thus, our aim is to develop, formulate and evaluate a single-vial lyophilized kit (EZYKit PSMA) for the preparation and radiolabeling of [68Ga]Ga-PSMA-11.

 Two commercially available [68Ge/68Ga] Generators used in this study were from ITG and Eckert & Ziegler with a current [68Ga]Gallium elution activity of 222 MBq and 1480 MBq, respectively. Initially, EZYkit-PSMA radiolabeling parameters were optimized, and the Glass Transition Temperature (Tg) of the optimized PSMA-11 formulation was determined. Quality assessment of EZYkit-PSMA, including physical appearance, quantitative assay of the active ingredient, radiochemical purity, pH, sterility, endotoxin, and storage stability, were also established.

 Optimization of radiolabeling parameters showed that the highest radiochemical purity was achieved with 0.35 ml and 0.75 ml of 1.5 M acetate buffer and 10 µg PSMA-11 for both ITG and Eckert & Ziegler Generator, respectively. The quality assessment results of EZYkit-PSMA were within the specifications except for the physical appearance, where it appears to be structurally collapsed. This study discussed two main factors that contributed to the collapsed lyophilized cake.

 Despite the physical appearance, EZYkit-PSMA was successfully developed, and the quality meets the pharmaceutical standards. EZYkit-PSMA showed high stability over 6 month's storage period in both the fridge and freezer. Overall, using EZYkit-PSMA for radiolabeling with [68Ga]Gallium simplified the whole radiolabeling procedure and reduces process time and error with high labelling yield and efficiency.

 [99mTc]Tc-MAG3 is one of the routine renal radiopharmaceuticals being used in nuclear medicine centers, throughout the world. This study investigated the synthesis and 99mTc-labeling of MAG3, as well as the synthesis of the S-acetyl-MAG3-NHS complexing agent, which was used for labeling bovine serum albumin (BSA) as a protein model using technetium-99m.

 S-acetyl-MAG3 was prepared by the reaction of S-acetyl thioglycolic acid and triglycine. It was also activated to its N-hydroxysuccinimide counterpart which was used for preparation of biomolecule conjugates. All compounds and intermediates were characterized by 1H NMR and LC/Mass spectroscopy.  Labeling of MAG3 with 99m-technetium was also well performed. The radiochemical purity and stability of labeled products was done by thin-layer chromatography. Also, biodistribution studies in mice was performed.

 The spectroscopic results confirmed the structure of compounds. The stability of [99mTc]Tc-MAG3  and [99mTc]Tc-MAG3-BSA was determined over 24h .It was found to drop from 90% to 60% and 99% to 80%,  respectively. There was no difference between serum and buffer results. Biodistribution studies for [99mTc]Tc-MAG3 confirmed renal excretion with injected dose per gram (%ID/g) kidney of 41.28 ± 4.70 , 45.63 ± 6.36 and 12.22 ± 2.83 after 1, 4 and 24h respectively.

 In this work, the rigorous purification processes were simplified through adjustment of molar ratios of reactants and the crude product obtained with higher yield was directly used for 99mTc labeling. The prepared labeled biomolecules conjugates showed acceptable radiochemical purity and stability. MAG3 was applicable for renal imaging according to biodistribution results.

 The study goal was to determine whether serial quantitative three phase [99mTc]Tc-MDP bone scintigraphy can provide additional information to accurately predict loosening in symptomatic patients after total knee arthroplasty (TKA) whose initial [99mTc]Tc-MDP study was not diagnostic.

 We retrospectively include bone scans of 125 patients suffering pain after knee arthroplasty. 52 patients with equivocal image findings on three phase planar bone scintigraphy and inconclusive clinical parameters were candidate for follow up examination. Quantification was performed on delayed planar views of both image series and the ratio of pathological peri-prosthetic tracer uptake to normal bone was evaluated. The change in periprosthetic abnormal to normal bone uptake ratios was analyzed within 6-months interval to assess. Interpretations were validated by clinical follow-ups or revision operation.

 Initial quantitative planar analysis in periprosthetic region did not relevantly enhance the diagnostic performance of bone scanning in assessing knee prosthetic loosening. Six months follow-up images improve the diagnostic power of bone scan but it was not statistically significant. However, a threshold of 3.9% rise in periprosthetic abnormal to normal bone uptake ratio of the "tibial plateau" within 6 months markedly improved the performance of three phase [99mTc]Tc-MDP  for the detection of loosening (sensitivity 87%, specificity 89%, p value = 0.002). 

 Equivocal scintigraphic findings are still a main challenge in management of TKA complications. Follow-up quantitative bone scan improves the diagnostic impact of bone scintigraphy for detection of loosening process in equivocal cases of TKA.

 Extrapulmonary manifestations of COVID-19 must not be neglected during the pandemic. Subacute thyroiditis is one of the possible complications people encounter during post-COVID-19 days. Thyroid scintigraphy and radioiodine uptake test help discriminate hyperthyroidism from destructive thyrotoxicosis. Finding a more precise way to diagnose subacute thyroiditis can help in the early detection and treatment of thyroid-related disorders.

 In this cross-sectional study, we evaluated 69 cases of COVID-19. Patients were divided into moderate and severe groups based on their clinical conditions. A thyroid scintigraphy scan was performed on the discharge day. Imaging was done 15-20 minutes after intravenous administration of 3-5 mCi of [99mTc]TcO4-. Scan findings were compared between moderate and severe groups and other participants' demographic and clinical features.

 In 69 patients, according to thyroid scintigraphy, 25 (36%) cases were reported as thyroiditis, and the rest were normal. There was no significant difference between the normal and subacute thyroiditis groups based on age, gender, past medical history, the severity of COVID-19, laboratory values and clinical signs and symptoms. Patients with subacute thyroiditis experienced palpitation and sore throat significantly higher than the normal group (P=0.002 and P=0.009, respectively).

 We conclude that patients admitted due to acute COVID-19 infection experiencing palpitation and sore throat can develop subacute thyroiditis more than others. Whereas the severity of the disease and laboratory testing were not diagnostic in subacute thyroiditis, thyroid scintigraphy may help in early detection.

 There are inconsistent results of studies on accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (2-[18F]FDG-PET/CT) for cervical lymph node (LN) staging. The aim of this study is to evaluate the accuracy of 2-[18F]FDG-PET/CT in the cervical LN staging of patients with papillary thyroid cancer (PTC) and the factors associated with false-positive LNs in these patients.

 A total of 234 patients with pathologically proven PTC, who underwent 2-[18F]FDG-PET/CT for staging from January 2011 to December 2014, were analyzed. The gold standard for diagnosing LN is a combination of surgical pathology and clinical follow-up. Nodal uptake with a maximum standardized uptake value (SUVmax) > 2.0 was interpreted as PET/CT-positive.

 The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 2-[18F]FDG-PET/CT in detecting cervical LN metastases were 42.7% (41/96), 77.7% (248/319), 36.6% (41/112), 81.9% (248/303), and 69.6% (289/415), respectively. The incidence of false-positive LN metastases was 63.4% (71 of 112 LNs). The factors significantly associated with false positives were age < 45 years old (p = 0.032) and SUVmax of the primary tumor < 4.0 (p = 0.021). In addition, false-positive LNs were correlated with a low LN SUVmax, location (central vs. lateral), and direction (ipsilateral vs. contralateral).

 These findings suggest that cervical LN staging by 2-[18F]FDG-PET/CT in PTC patients should be more carefully assessed in patients younger than 45 years old with a primary tumor SUVmax < 4.0 or contralateral LN.

A 56-year-old woman with new-onset aphasia and mood changes was diagnosed with a left temporal mass. The surgery was done. She was referred for a trial of post-operative study of in vivo evaluation of CXCR4 expression using [68Ga]Ga-Pentixafor (Pars-CixaforTM) PET/CT in high-grade glioma. The imaging from the brain revealed no evidence of tumoral remnant. Furthermore, the patient represented positive COVID-19 PCR about 4 weeks prior to the study. Surprisingly, mild diffuse uptake was noted in the base and periphery of both lungs with ground glass opacities (GGO) and consolidations (SUVmax = 2.60) with CXCR4-avid hilar lymph nodes (SUVmax up to 3.42).

We report a patient with locally invasive metastatic castration resistant prostate adenocarcinoma, which had massive invasion to the bladder and caused frequent gross hematuria. The patient had received more than 10 units of packed cell at the time he was referred for [177Lu]Lu-PSMA-617 therapy, but despite frequent transfusions his serum hemoglobin level had been under 8 g/dl most of the time. He had received first generation androgen deprivation therapy (ADT) from 3 years previously and the second generation since 1 year ago and had undergone multiple procedures for cessation of hematuria, such as multiple cystoscopies, bladder irrigations and angioembolizations. We performed [99mTc]Tc-PSMA whole body and SPECT/CT scan, which demonstrated a large PSMA avid prostate mass invading the urinary bladder wall. All components of the locally invasive tumor were present demonstrating high PSMA avidity, so he was scheduled for [177Lu]Lu-PSMA-617 therapy. One week after the diagnostic scan, therapeutic dose of [177Lu]Lu-PSMA-617 was administered. The patient reported no hematuria 4 days after the [177Lu]Lu-PSMA-617 administration. In the follow up, no recurrent hematuria was reported, too. The PSA level also declined from 40.5 ng/ml to 18.7 ng/ml, 1 month after the first treatment.

Thyroglobulin elevated-negative iodine scintigraphy (TENIS) differentiated thyroid cancer (DTC) patients are a subgroup of DTC patients with almost rapid disease progression and reduced overall survival and them usually do not have an effective treatment modality. Surgery and metastatectomy is the best option for recurrent disease in cases of solitary or oligometastasis. Detection of the metastatic sites is of utmost importance in these patients. We present a patient with TENIS syndrome and negative [18F]FDG PET/CT and [68Ga]Ga-DOTATATE whole body PET/CT scan in whom just [68Ga]Ga-FAPI PET/CT helped in localizing the metastatic lesion to the iliac bone and subsequently the bone metastasis was resected and the pathology report confirmed the diagnosis.