davood beiki

[68Ga]Ga-PSMA PET/CT has gained acceptance for localizing local and distant metastases; However, urinary activity remains a confounding factor in interpreting local metastases. The aim of this study was to evaluate the diagnostic value of two-phase protocol (i.e., early and regular imaging, TPP) in comparison with delayed optimized protocol (i.e., combined regular and delayed post hydration and diuresis images, DOP) to detect locoregional prostatic metastases. Forty-one prostate cancer patients referred for staging (n = 12) or the evaluation of rise in PSA level in prostate cancer (n = 29) were prospectively assessed. In this study, each patient received an early 5-10 min image from pelvic region for two bed position, regular (RP) (60 min) and finally delayed static images. The scan findings were characterized as positive, negative or equivocal. The diagnostic significance of TPP was compared with DOP for prostatic, periprostatic, locoregional lymph nodes and pelvic bone involvement. The diagnostic agreement between DOP and TPP for prostate/prostate bed lesions was comparable with the agreement of DOP and RP (Kappa: 0.78, p < 0.001) vs. (Kappa: 0.8, p value < 0.001). TPP in comparison with RP, had superior sensitivity for prostate/prostate bed lesions (95% vs. 80%). The sensitivity for lymph node metastases, extraprostatic extension and osteometastases was identical between the two protocols. TPP has the potential to replace DOP for the evaluation of prostate/prostate bed lesions; however, there remains instances where delayed imaging is helpful in characterizing the anatomic abnormality especially in the lymph node region.

  To compare the diagnostic performance of [68Ga]-Ga-FAPI-46 and [18F]-FDG PET/CT imaging for the detection of lesions and disease staging in breast cancer.

Twelve female patients with breast cancer (mean age= 49.2±13.29 years) and previous [18F]-FDG PET/CT were recruited in the study. [68Ga]Ga-FAPI-46 imaging performed in all patients within one month after [18F]-FDG PET/CT imaging. The acquired PET/CT data with both tracers were reconstructed. Tracer avid lesions with each PET tracer were identified and the semi-quantitative parameters i.e. SUVmax, lesion counts and target-to-background ratio (TBRmax) were analyzed.

Physiologic distribution of [68Ga]-Ga-FAPI-46 was observed in the liver, blood pool and kidneys, whereas no tracer uptake was noted in the brain and heart. The mean liver SUVmax for [68Ga] Ga-FAPI-46 was 1.5±0.1 which was lower than that noted for [18F]-FDG PET/CT (2.9±0.2). Likewise, the mean blood pool SUVmax value for [68Ga]-Ga-FAPI-46 was lower than [18F]-FDG PET/CT (1.7±0.1 versus 2.0±0.1). [68Ga]-Ga-FAPI-46 PET/CT demonstrated higher tracer uptake in the lesions detected in the brain, bone, internal mammary and lymph nodes in 4/12 patients. The overall lesions detections and the mean SUVmax values did not differ significantly between the two techniques. On the other hand, [68Ga]-Ga-FAPI-46 demonstrated higher mean TBRmax than [18F] FDG PET/CT particularly for lesions detected in kidneys, chest wall, mediastinum, and musculoskeletal lesions. However, both techniques offered identical TNM staging.

The findings of this preliminary study demonstrated that [68Ga]-Ga-FAPI-46 and [18F]-FDG PET/CT offered identical disease staging in the breast cancer patients. [68Ga]-Ga-FAPI-46 showed lower liver and blood pool uptake and an enhanced tumor-to-background ratio, thereby suggesting its potential for improved lesions detection. This may open opportunity for emerging FAP based radioligand for therapeutic applications in advanced stage breast cancers. However, this needs validation in a larger number of patients.

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.

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.

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.

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.

Thyroid cancer is the most common endocrine malignancy in the world; however, these patients usually experience a high survival rate if they receive appropriate and timely treatment. Meanwhile, patients classified as having differentiated thyroid cancer with high thyroglobulin and negative iodine scan [Differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy (TENIS)] are always considered a diagnostic-therapeutic challenge.

We conducted a comprehensive literature search of published papers in the PubMed/MEDLINE database regarding nuclear imaging in differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy. We included all human studies in this field.

In this review, we examined four major groups of imaging studies aimed at identifying GLUT, SSTR, PSMA and FAP receptors in patients with TENIS. The diagnostic rate of 2-[18F]FDG PET/CT in these patients has been reported as 63-81% based on various studies. Also, [68Ga]Ga-DOTATATE PET/CT, [68Ga]Ga-PSMA PET/CT and [68Ga]Ga-FAPI PET/CT scans have shown good results in these patients.

[68Ga]Ga-FAPI PET/CT imaging has the highest diagnostic rate among these patients. Given the theranostic capability of FAPI and the numerous complications and limited inclusion criteria for treatment with tyrosine kinase inhibitors, it has been the next step in the treatment of patients with TENIS. Therefore, more extensive studies in this field are warranted.

2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (2-[18F]FDG-PET/CT) is implemented in papillary thyroid cancer (PTC) patients with elevated Thyroglobulin (Tg) and negative Iodine-131 whole-body scan (131I-WBS). Here, we evaluated the impact of TSH stimulation after levothyroxine withdrawal on the detection rate of 2-[18F]FDG-PET/CT. A prospective study was performed on 60 PTC patients, presented with negative 131I-WBS and elevated or unjustifiably high Tg. 2-[18F]FDG-PET/CT was performed in 30 patients while they were on levothyroxine therapy (unstimulated-TSH [uns-TSH]) and after Levothyroxine withdrawal in the other 30 patients (stimulated-TSH [s-TSH]). Results of the two groups were compared using nonparametric tests. Receiver operating characteristic curve was used to find Tg cutoff values for predicting positive scan results. Overall, 2-[18F]FDG-PET/CT was positive in 63.3% of the patients, 80% (24/30) in s-TSH and 46.7% (14/30) in uns-TSH group. The detection rate was higher in s-TSH group (p=0.007). It was still significant in multiple regression analysis (p=0.041). In uns-TSH group, 2-[18F]FDG-PET/CT was more often positive in patients with higher uns-Tg level (p=0.002). An uns-Tg level of ≥19.00 ng/mL predicted positive results with the sensitivity of 0.786 and specificity of 0.750 (area under curve=0.819). Although statistically insignificant (p=0.055), s-Tg was higher in patients with positive 2-[18F]FDG-PET/CT studies in the s-TSH group. No relation was demonstrated between TSH and anti-Tg-antibody levels and 2-[18F]FDG-PET/CT positivity. TSH-stimulation after levothyroxine withdrawal might enhance the detection rate of 2-[18F]FDG-PET/CT in PTC patients. Additionally, 2-[18F]FDG-PET/CT is more often positive in patients with higher Tg levels.

Targeted radionuclide therapy with [177Lu]Lu-prostate-specific membrane antigen (PSMA) has shown promising results for the treatment of castration-resistant prostate cancer (mCRPC). Nevertheless, a proportion of patients do not respond to this therapy. Here, we aimed to evaluate the prognostic significance of the pretreatment pathologic and laboratory factors for the prediction of biochemical response to the first cycle of [177Lu]Lu-PSMA therapy. In this retrospective study, mCRPC patients, referred for [177Lu]Lu-PSMA therapy, were included. We retrieved the data of patients, undergone [177Lu]Lu-PSMA, from March 2019 to March 2021. Multiple baseline pathologic and laboratory parameters were extracted and correlated with the response to the first cycle. The prostate-specific antigen (PSA) level was evaluated six weeks after [177Lu]Lu-PSMA therapy for the biochemical response. Forty-three patients with a mean age of 69.8±10.2 were included. Bone and visceral metastases were present in 81.4% and 14.0% of the patients, respectively. Except for two, all patients had received hormone- and chemotherapy. The mean PSA level was 189.9±259.0 at baseline. Following one cycle of [177Lu]Lu-PSMA, “≥ 10% PSA response” and “≥ 50% PSA response” were seen in 81.4% and 44.2% of the patients, respectively. Patients with higher baseline PSA more frequently had ≥ 10% PSA response (p= 0.004). Also, the reduction in the PSA level correlated with baseline PSA (p=0.013, r=0.375). [177Lu]Lu-PSMA therapy results in the biochemical response in a considerable number of patients after one cycle. In nearly half of patients, PSA declines more than 50%. Higher baseline PSA is correlated with the level of PSA response.

Here, we describe a patient with a history of colorectal cancer in whom 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) was performed for the evaluation of response to therapy. [18F]FDG PET/CT showed a small residual disease in the rectum. In addition, multiple metabolically inactive soft tissue densities were demonstrated in the left hemithorax and the left upper abdominal region, previously interpreted as metastases on computed tomography. Furthermore, bizarre-shaped soft tissues were visualized in the anatomical location of the spleen. Hence, splenosis was suspected. Subsequently, the patient underwent [99mTc]Tc-denatured red blood cell ([99mTc]Tc-DRBC) scintigraphy, which confirmed the diagnosis of extensive thoracoabdominal splenosis.

Adrenal lesions are commonly observed during 18F-FDG PET/CT studies. Although, most of these lesions are considered benign, an important consideration in oncologic patients is metastasis. Benign lesions, such as adenomas usually present with low 18F-FDG uptake, although overlap with malignant lesions exist and clear SUV cut-off for distinguishing adrenal adenomas has not been established. Different criteria have been proposed to further characterize adrenal lesions, as benign or metastatic. Conventional imaging modalities have additional value when the degree of uptake is equivocal. In this review, we go through some of the common adrenal lesions, as well as discerning features that favor either benign or malignant etiology.

Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa . Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55–83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo. DOTA conjugated antagonistic peptide with the sequence of p-Cl-Phe-Cyclo(D-Cys-L-BzThi-D-Aph-Lys-Thr-Cys)-D-Tyr-NH2 (DOTA-Peptide 2) was labeled with 177Lu. In vitro assays (saturation binding assay and internalization test) and animal biodistribution were performed in human colon adenocarcinoma cells (HT-29) and HT-29 tumor-bearing nude mice. 177Lu-DOTA-Peptide 2 showed high stability in acetate buffer and human plasma (>97%). Antagonistic property of 177Lu-DOTA-Peptide 2 was confirmed by low internalization in HT-29 cells (<5%). The desired dissociation constant (Kd =11.14 nM) and effective tumor uptake (10.89 percentage of injected dose per gram of tumor) showed high binding affinity of 177Lu-DOTA-Peptide 2 to somatostatin receptors.  177Lu-DOTA-Peptide 2 demonstrated selective and high binding affinity to somatostatin receptors overexpressed on the surface of HT-29 cancer cells, which could make this radiopeptide suitable for somatostatin receptor-targeted radionuclide therapy.

Differentiatedthyroid carcinoma (DTC) constitute approximately 90% of all thyroid tumors with an overall excellent prognosis. However, there is a small group of patients with a more aggressive form of disease, usually associated with certain poor prognostic factors. Using our large database of patients with DTC, the current study aims at identifying some of these factors. 

This retrospective study was based on the registry of patients with non-medullary thyroid carcinoma. Data were collected on the clinical, laboratory, and outcome characteristics of 501 patients followed at our department.

On multivariate analysis, the following variables were predictive of persistent disease: less than total thyroidectomy, residual disease on the post treatment whole body radioiodine scan (WBIS), higher received radioiodine activities, and higher levels of baseline stimulated thyroglobulin (Tg) and thyroid stimulating hormone (TSH). The greatest predictive value for the persistent/recurrent disease was attributed to the presence of residual disease on the post-treatment WBIS (odds ratio (OR): 33.72, 95% confidence interval (95% CI): 18.17-62.57), followed by type of surgical procedure (OR: 8.92, 95% CI: 2.90-27.39), radioiodine ablation dose (OR: 4.03, 95% CI: 1.56-10.39), stimulated baseline Tg level (OR: 2.79, 95% CI: 1.53-5.08) and finally, the stimulated baseline TSH level (OR: 2.21, 95% CI: 1.08-4.519).

In patients with DTCs, surgical procedures other than total thyroidectomy, presence of residual disease on the post-treatment WBIS, higher received radioiodine activities, higher baseline stimulated Tg and TSH levels are associated with a higher probability of having persistent disease and can be used in conjunction with other disease characteristics to reach proper decisions with regard to treatment and follow-up.

68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs.

Twenty-five patients (males:females=8:17; age range=2–71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant.

This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

Localization of 99mTc- hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) by parathyroid adenomas is well known, and this warrants MIBI scan to evaluate suspected parathyroid adenoma in primary hyperparathyroidism. Typically, the radionuclide concentrates in both the thyroid gland and parathyroid adenoma in early images, and later on delayed images washes out slowly from the parathyroid adenomas located in the neck or mediastinum, in comparison with more rapid wash out from the thyroid gland. We report a 71-year old woman with history of hypothyroidism, who has been on levothyroxine therapy for 5 years, and primary hyperparathyroidism, for which a double phase 99mTc-MIBI parathyroid scintigraphy was performed. Although the planar views demonstrated no evidence of radiotracer uptake in thyroid gland, single photon emission computed tomography/computed tomography (SPECT-CT) images revealed the presence of thyroid gland with a multinodular pattern on CT component of the study. Also planar images showed no focal uptake, but in SPECT-CT evaluation a MIBI-avid nodule was depicted in the posteromedial aspect of lower portion of left thyroid lobe, representing a parathyroid adenoma, later confirmed by pathology after surgical resection. The possible explanation for non-visualization of thyroid gland could be thyroid suppression with levothyroxine.

In view of somatostatin receptor (SSR) expression on cell membranes of the majority of neuroendocrine tumors (NETs), functional imaging exploiting analogs of SSR alongside the anatomical imaging is the mainstay of this diagnostic modality. In this prospective study, we assessed and directly compared the diagnostic parameters of 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT, as well as CT/MRI. Twenty-five NET patients, either histologically proven or highly suspicious for NET, who were referred for Octreotide Scan were enrolled in this prospective study. They all underwent 99mTc-Octreotide SPECT/CT and then 68Ga-DOTATATE PET/CT. A blind interpretation was conducted for each imaging as well as for the previously obtained conventional imaging (CT or MRI). The patient-based and lesion-based analysis were conducted and the results of the three modalities were compared. The histopathologic confirmation or follow-up data were considered as the gold standard. Also, the impact of 68Ga-DOTATATE PET/CT on the patient’s management was assessed. Overall, 77 lesions in 14 patients, 135 in 19 and 86 in 16 were detected on 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. On patient-based analysis, the sensitivity was 65%, 90% and 71% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. Also, the specificity was 80%, 80% and 75% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. The correlation between 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT results was significant (P=0.02; kappa value=0.57), no correlation, however, was depicted with CI (P=0.07; kappa value=0.35). On lesion-based analysis, 68Ga-DOTATATE PET/CT found more organs (P=0.02) and lesions (P=0.001) in comparison with 99mTc-Octreotide SPECT/CT and also more lesions in comparison with CT/MRI (P=0.003). In addition, comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT revealed more data in 44% and 36% of the patients, resulting in management modification in 24% and 20%, respectively. Comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga- DOTATATE PET/CT provided more sensitivity and specificity in patients with NETs showing more involved organs as well as tumoral lesions. Also, 68Ga-DOTATATE PET/ CT led to change of management in up to one-fourth of the patients, especially in a sub-group re-evaluated for recurrence.

The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys(OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.

The present study was aimed to assess the diagnostic performance of the two imaging methods of 131I-metaiodobenzylguanidine (131I-MIBG) and 99mTc-hydrazinonicotinyl-Tyr3-Octreotide (99mTc-HYNIC-TOC) in diagnosis and localization of pheochromocytoma and neuroblastoma.
This study was conducted on 40 consecutive patients with positive pathological results for pheochromocytoma or neuroblastoma. The patients underwent both I-131 131I-MIBG and octreotide scintigraphies. By using the findings of cytopathology, biomarkers, imaging studies, as well as the results of a six-month follow-up, a composite reference standard (CRS) was defined as the diagnostic gold standard.
Overall comparison of these two agents revealed higher sensitivity for 131I-MIBG than octreotide study both in patient-based analysis (100% vs. 80.9%, respectively), and lesion-based analysis (94.4% vs. 80.56%, respectively). In pheochromocytoma 131I-MIBG and octreotide are both highly sensitive (100%), while 131I-MIBG is more specific (100% vs. 87.5%). In neuroblastoma, 131I-MIBG is more sensitive than octreotide (100% vs. 81.25%).
Our study shows superiority of 131I-MIBG over octreotide scanning in detection of both neuroblastoma and pheochromocytoma lesions. However, a combination of these two diagnostic tools provides more complete information on the nature and the site of lesions. The first suggested study is 131I-MIBG scanning, and if it is not available, or detecting precise location of all lesions is of concern, octreotide scanning can be helpful as a complementary study. Furthermore, in case of octreotide positive lesions, follow-up can be performed with octreotide scan with less radiation burden.

Myocardial perfusion imaging (MPI) is an important imaging modality in managing patients with cardiovascular disease. MPI has a significant role in diagnosis and management of cardiovascular disease; however it is subjected to different artifacts. Combining pharmacologic stress with submaximal exercise reduces side effects, improves image quality, and enhances the detection of ischemia, compared with suboptimal exercise or vasodilator stress alone.
97 patients (62 males and 35 females) which were randomly allocated into two groups were studied using gated single-photon emission computed tomography (SPECT) imaging. The patients were randomly allocated into two different groups: dipyridamole or dipyridamole combined with submaximal exercise group. Subsequently, they were imaged at 15, 60, 120, and 180 minutes after radiotracer injection.
97 patients with an average age of 57.1 were compared 15, 60, 120 and 180 minutes after radiotracer injection. Comparing dipyridamole and dipyridamole submaximal exercise group a significant difference in target areas (myocardium, inferior and lateral wall) count ratio to both liver and colon count ratio was observed (P A protocol that combines submaximal exercise with dipyridamole stress is highly effective in improvingthe average count ratio of myocardial walls compared to visceral activity.

Malignant melanoma is the most lethal type of skin cancers with unfavorable prognosis. Alpha-MSH peptide analogues have a high affinity for melanocortine-1 (MC1) receptors on melanocytes over expressing in malignant melanoma cells. Pre-clinical studies have shown promising results for radiolabeled MSH imaging in this malignancy. The purpose of this study is to assess the diagnostic value of 99mTc-α-MSH imaging in malignant melanoma.
Twenty-one patients (13 men) with pathologically confirmed malignant melanoma with or without metastatic distribution were included in this study. 740-1110 MBq 99mTc-α-MSH was injected and whole body scans were performed 20, 120 and 240 minutes post injection and were assessed both qualitatively and semi-quantitatively using target (T) to background (BG) ratio.
The T/BG ratio for the primary tumor bed was 2.51±2.26, 2.56±2.48 and 1.92±1.79 minutes in the whole body scans 20, 120 and 240 minutes post injection, respectively. The sensitivity, specificity, negative and positive predictive values were 75%, 80%, 50% and 92% for primary lesion and 25%, 100%, 68% and 100% for distant metastasis, respectively.
99mTc-α-MSH is a newly introduced agent for diagnosis of tumoral lesions in malignant melanoma. Our study showed a high sensitivity with this modality in primary lesions as well as lymph node involvements. However the detection rate was not high in distant metastasis. The preliminary results are promising especially as a new complementary imaging method in management of malignant melanoma.

Studies have indicated advantageous properties of [DOTA-DPhe1 , Tyr3 ] octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is the second leading cause of cancer mortality in women, and most of these cancers are often an adenocarcinoma. Due to the importance of target to non-target ratios in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an adenocarcinoma breast cancer animal model was studied in this research, and the optimized time for imaging was determined.
68Ga was obtained from 68Ge/68Ga generator. The complex was prepared at optimized conditions. Radiochemical purity of the complex was checked using both HPLC and ITLC methods. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer. Also, PET/CT imaging was performed up to 120 min post injection.
The complex was produced with radiochemical purity of greater than %98 and specific activity of about 40 GBq/mM at optimized conditions. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer indicated fast blood clearance and significant uptake in the tumor. Significant tumor:blood and tumor:muscle uptake ratios were observed even at early times postinjection. PET/CT images were also confirmed the considerable accumulation of the tracer in the tumor.
Generally, the results proved the possible application of the radiolabelled complex for the detection of the adenocarcinoma breast cancer and according to the pharmacokenitic data, the suitable time for imaging was determined as at least 30 min after injection.