Amino-modified-silica-coated gadolinium-copper nanoclusters, conjugated to AS1411 aptamer and radiolabeled with technetium-99 m as a novel multimodal imaging agent.

Hybridimagingtechnology has the potential to provide reliable imagingand accurate detection of cancer cells by combining the advantages and overcoming the shortages of various clinical imaging tools. Nanomaterials with unique targeting properties and their small size have improved biomedical imaging. Indeed, their small size determines local contrast agent concentrations in tumors by enhanced permeability and retention (EPR) effect. In this work, amino-modified silica-coated Gadolinium-Copper Nanoclusters were fabricated and conjugated to AS1411 aptamer (Apt-ASGCuNCs) and radiolabeled with technetium-99 m (99mTc) for in vivo fluorescence imaging, magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). The synthesized nanoconjugate was fully characterized by transmission electron microscopy (TEM), element mapping, fluorescence spectroscopy, and Fourier-transform infrared spectroscopy. Moreover, XTT assay, and apoptosis and necrosis methods were applied to study toxicity. Radiochemical yield was calculated 93% that revealed a great potential for complex formation between Apt-ASGCuNCs and 99mTcO4-. Also, good stability of 99mTc-Apt-ASGCuNCs was found in the human serum up to 4 h. Both Apt-ASGCuNCs and 99mTc-Apt-ASGCuNCs indicated a considerable tumor-targeting in in vivo fluorescence imaging, MRI and SPECT with 4T1 tumor-bearing BALB/c mice. The biodistribution results showed no undesirable accumulation of 99mTc-Apt-ASGCuNCs in the liver, and spleen as it circulated freely in the blood pool. Meanwhile, 99mTc-Apt-ASGCuNCs were removed from the body through the renal clearance system, making it more convenient for future multimodality imaging applications.

Design of peptide-based inhibitor agent against amyloid-ß aggregation: Molecular docking, synthesis and in vitro evaluation.

Formation of the amyloid beta (Aß) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. ß-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. According to the obtained interactions and binding energy from docking, the best-designed peptide (d-GABA-FPLIAIMA) was chosen and synthesized in great yield (%96) via the Fmoc solid-phase peptide synthesis. The synthesis and purity of the resulting peptide were estimated and evaluated by Mass spectroscopy and Reversed-phase high-performance liquid chromatography (RP-HPLC) methods, respectively. Stability studies in plasma and Thioflavin T (ThT) assay were performed in order to measure the binding affinity and in vitro aggregation inhibition of Aß peptide. The d-GABA-FPLIAIMA peptide showed good binding energy and affinity to Aß fibrils, high stability (more than 90%) in human serum, and a reduction of 20% in inhibition of the Aß aggregation growth. Finally, the favorable characteristics of our newly designed peptide make it a promising candidate ß-sheet breaker agent for further in vivo studies.

177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study.

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80-85% of death. αvß3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of αvß3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK)2 with 177Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of -3.878 was obtained for 177Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (Kd) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing αvß3 integrin receptors.

Design, synthesis, radiolabeling and biological evaluation of new urea-based peptides targeting prostate specific membrane antigen.

Early diagnosis of Prostate cancer (PCa) plays a vital role in successful treatment increasing the survival rate of patients. Prostate Specific Membrane Antigen (PSMA) is over-expressed in almost all types of PCa. The goal of present study is to introduce new 99mTc-labeled peptides as a PSMA inhibitor for specific detection of PCa at early stages. Based on published PSMA-targeting compounds, a set of peptides bearing the well-known Glu-Urea-Lys pharmacophore and new non-urea containing pharmacophore were designed and assessed by in silico docking studies. The selected peptides were synthesized and radiolabeled with 99mTc. The in-vitro tests (log P, stability in normal saline and fresh human plasma, and affinity toward PSMA-positive LNCaP cell line) and in-vivo characterizations of radiopeptides (biodistribution and Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging in normal and tumour-bearing mice) were performed. The peptides 1-3 containing Glu-Urea-Lys and Glu-GABA-Asp as pharmacophores were efficiently interacted with crystal structure of PSMA and showed the highest binding energies range from -8 to -11.2 kcal/mol. Regarding the saturation binding test, 99mTc-labeled peptide 1 had the highest binding affinity (Kd = 13.58 nM) to PSMA-positive cells. SPECT-CT imaging and biodistribution studies showed high kidneys and tumour uptake 1 h post-injection of radiopeptide 1 and 2 (%ID/g tumour = 3.62 ± 0.78 and 1.8 ± 0.32, respectively). 99mTc-peptide 1 (Glu-urea-Lys-Gly-Ala-Asp-Naphthylalanine-HYNIC-99mTc) exhibited the highest binding affinity, high radiochemical purity, the most stability and high specific accumulation in prostate tumour lesions. 99mTc-peptide 1 being of comparable efficacy and pharmacokinetic properties with the well-known PET tracer (68Ga-PSMA-11) seems to be applied as a promising SPECT imaging agent to early diagnose of PCa and consequently increase survival rate of patients.

Synthesis, biological evaluation and preclinical study of a novel 99mTc-peptide: A targeting probe of amyloid-ß plaques as a possible diagnostic agent for Alzheimer's disease.

With respect to the main role of amyloid-ß (Aß) plaques as one of the pathological hallmarks in the brain of Alzheimer's patients, the development of new imaging probes for targeted detection of Aß plaques has attracted considerable interests. In this study, a novel cyclopentadienyl tricarbonyl Technetium-99 m (99mTc) agent with peptide scaffold, 99mTc-Cp-GABA-D-(FPLIAIMA)-NH2, for binding to the Aß plaques was designed and successfully synthesized using the Fmoc solid-phase peptide synthesis method. This radiopeptide revealed a good affinity for Aß42 aggregations (Kd = 20 µM) in binding affinity study and this result was confirmed by binding to Aß plaques in brain sections of human Alzheimer's disease (AD) and rat models using in vitro autoradiography, fluorescent staining, and planar scintigraphy. Biodistribution studies of radiopeptide in AD and normal rats demonstrated a moderate initial brain uptake about 0.38 and 0.35% (ID/g) 2 min post-injection, respectively. Whereas, AD rats showed a notable retention time in the brain (0.23% ID/g at 30 min) in comparison with fast clearance in normal rat brains. Normal rats following treatment with cyclosporine A as a p-glycoprotein inhibitor showed a significant increase in the radiopeptide brain accumulation compared to non-treated ones. There was a good correlation between data gathered from single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and biodistribution studies. Therefore, these findings showed that this novel radiopeptide could be a potential SPECT imaging agent for early detection of Aß plaques in the brain of patients with AD.

Design, preparation and biological evaluation of a 177Lu-labeled somatostatin receptor antagonist for targeted therapy of neuroendocrine tumors.

Somatostatin receptor-targeted radionuclide therapy has become an effective treatment in patients with neuroendocrine tumors. Recently, investigations on the development of antagonistic peptides are increasing with possible superior biological properties as opposed to the agonists. Herein, we have reported the development of a new somatostatin receptor peptide ligand labeled with 177Lu to achieve a therapeutic ligand for tumor treatment. The interactions of selected and drown ligands using Avogadro software were docked on somatostatin receptor by Dink algorithm. The best docked peptide-chelator conjugate (DOTA-p-Cl-Phe-Cyclo(d-Cys-l-BzThi-d-Aph-Lys-Thr-Cys)-d-Tyr-NH2) (DOTA-Peptide 2) was synthesized using the Fmoc solid-phase method. DOTA-Peptide 2 was radiolabeled with the 177Lu Trichloride (177LuCl3) solution at 95 °C for 30 min and radiochemical purity (RCP) of 177Lu-DOTA-Peptide 2 solution was monitored by radio-HPLC and radio-TLC procedures. The new radiolabeled peptide was evaluated for stability, receptor binding, internalization, biodistribution and single-photon emission computed tomography (SPECT) imaging using C6 glioma cells and C6 tumor-bearing rats. DOTA-Peptide 2 was obtained with 98% purity and efficiently labeled with 177Lu (RCP > 99%). 177Lu-DOTA-Peptide 2 showed a high value of stability in acetate buffer (91.4% at 312 h) and human plasma (>97% at 24 h). Radioconjugate exhibited low internalization (<5%) and high affinity for somatostatin receptors (Kd = 12.06 nM, Bmax = 0.20 pmol/106 cells) using saturation binding assay. Effective tumor uptake of 7.3% ID/g (percentage of injected dose per gram of tumor) at 4 h post-injection and fast clearance of radiopeptide from blood and other organs led to a high tumor-to-normal organ ratios. SPECT/CT imaging clearly showed the activity localization in tumor. The favorable antagonistic properties of 177Lu-DOTA-Peptide 2 on the somatostatin receptors can make it a suitable candidate for peptide receptor radionuclide therapy (PRRT). In the future study, the therapeutic application of this radiopeptide will be evaluated.

The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I-MIBG accompanied by ASCT for high-risk and relapsed neuroblastoma: a pilot study.

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant (131) I-MIBG scintigraphy. Twenty high-risk patients were enrolled. On day -30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG-avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m2), carboplatin (1500 mg/m2), and melphalan (210 mg/m2). Non-MIBG-avid subgroup received etoposide (600 mg/m2), carboplatin (1200 mg/m2), and melphalan (150 mg/m2). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17-65) in MIBG-avid and 38.9 months (range, 18-65) in non-MIBG-avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG-avid patients, the three-yr OS was 66 ± 21%. In MIBG-non-avid subgroup, the three-yr OS was 53 ± 20%. In MIBG-avid and non-MIBG-avid subgroups, the three-yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre-ASCT MIBG scintigraphy in high-risk neuroblastoma. MIBG-avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.

Recent Clinical Implications of FAPI: Imaging and Therapy.

ABSTRACT: The fibroblast activation protein (FAP) is a biomarker that is selectively overexpressed on cancer-associated fibroblasts (CAFs) in various types of tumoral tissues and some nonmalignant diseases, including fibrosis, arthritis, cardiovascular, and metabolic diseases. FAP plays a critical role in tumor microenvironment through facilitating proliferation, invasion, angiogenesis, immunosuppression, and drug resistance. Recent studies reveal that FAP might be regarded as a promising target for cancer diagnosis and treatment. FAP-targeted imaging modalities, especially PET, have shown high sensitivity and specificity in detecting FAP-expressing tumors. FAP-targeted imaging can potentially enhance tumor detection, staging, and monitoring of treatment response, and facilitate the development of personalized treatment strategies. This study provides a comprehensive view of FAP and its function in the pathophysiology of cancer and nonmalignant diseases. It also will discuss the characteristics of radiolabeled FAP inhibitors, particularly those based on small molecules, their recent clinical implications in imaging and therapy, and the associated clinical challenges with them. In addition, we present the results of imaging and biodistribution radiotracer 68Ga-FAPI-46 in patients with nonmalignant diseases, including interstitial lung disease, primary biliary cirrhosis, and myocardial infarction, who were referred to our department. Our results show that cardiac FAP-targeted imaging can provide a novel potential biomarker for managing left ventricle remodeling. Moreover, this study has been organized and presented in a manner that offers a comprehensive overview of the current status and prospects of FAPI inhibitors in the diagnosis and treatment of diseases.

Exploring innovative strides in radiolabeled nanoparticle progress for multimodality cancer imaging and theranostic applications.

Multimodal imaging unfolds as an innovative approach that synergistically employs a spectrum of imaging techniques either simultaneously or sequentially. The integration of computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and optical imaging (OI) results in a comprehensive and complementary understanding of complex biological processes. This innovative approach combines the strengths of each method and overcoming their individual limitations. By harmoniously blending data from these modalities, it significantly improves the accuracy of cancer diagnosis and aids in treatment decision-making processes. Nanoparticles possess a high potential for facile functionalization with radioactive isotopes and a wide array of contrast agents. This strategic modification serves to augment signal amplification, significantly enhance image sensitivity, and elevate contrast indices. Such tailored nanoparticles constructs exhibit a promising avenue for advancing imaging modalities in both preclinical and clinical setting. Furthermore, nanoparticles function as a unified nanoplatform for the co-localization of imaging agents and therapeutic payloads, thereby optimizing the efficiency of cancer management strategies. Consequently, radiolabeled nanoparticles exhibit substantial potential in driving forward the realms of multimodal imaging and theranostic applications. This review discusses the potential applications of molecular imaging in cancer diagnosis, the utilization of nanotechnology-based radiolabeled materials in multimodal imaging and theranostic applications, as well as recent advancements in this field. It also highlights challenges including cytotoxicity and regulatory compliance, essential considerations for effective clinical translation of nanoradiopharmaceuticals in multimodal imaging and theranostic applications.

Novel Gd-DTPA-peptide for targeted breast tumor magnetic resonance imaging.

The prevalence of breast cancer underscores the imperative for early diagnosis in guiding treatment decisions. This study introduces a novel contrast agent, Gd-DTPA-VGB3, derived from the peptide VGB3 targeting vascular endothelial growth factor receptor-1 (VEGFR1) and VEGFR2, to enhance the contrast of conventional drug Magnevist in breast tumor MRI. The MRI contrast agent was synthesized on rink amide resin via Fmoc strategy, incorporating amino acids, and coupling to diethylenetriaminepentaacetic acid (DTPA). Gadolinium (Gd)-DTPA-VGB3 displayed specific binding to VEGFR1/2 in a displacement binding assay. Gd-DTPA-VGB3 exhibited minimal cytotoxicity to normal MCF-10 cells while inhibiting 4T1 mammary carcinoma cell proliferation. Compared to Magnevist, Gd-DTPA-VGB3 demonstrated a 2.8-fold increase in contrast-to-noise ratio (CNR) (355 vs. 125). Gd-DTPA-VGB3 exhibited enhanced accumulation in 4T1 tumor-bearing mice, resulting in significant signal intensity improvement. The findings highlight Gd-DTPA-VGB3's specific binding to VEGFRs, substantiating its potential as a candidate for enhancing MRI contrast in breast cancer diagnostics.

Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer.

As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient's chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression.

Diagnostic value of [ 68 Ga]Ga-Pentixafor PET/CT in malignant melanoma: a pilot study.

OBJECTIVE: To evaluate the diagnostic value of [ 68 Ga] Ga-Pentixafor in malignant melanoma patients. METHODS: In this prospective study, patients with histology-proven melanoma were included and underwent [ 18 F]fluoro-D-glucose ([ 18 F]FDG) and [ 68 Ga] Ga-Pentixafor PET/computed tomography (CT) within a week. Suspicious lesions were interpreted as benign vs. malignant, and the corresponding semi-quantitative PET/CT parameters were recorded and compared. RESULTS: Twelve consecutive melanoma patients (mean age: 60 ±â€…6) were included. Two patients were referred for initial staging, two for detecting recurrence and eight for evaluating the extent of metastases. Overall, [ 18 F]FDG PET/CT showed 236 tumoral lesions, including two primary tumors, two recurrent lesions, 29 locoregional metastases and 203 distant metastases. In [ 68 Ga]Ga-Pentixafor PET/CT, 101 tumoral lesions were detected, including two primary tumors, one recurrence, 16 locoregional metastases and 82 distant metastases. Notably, a documented brain metastasis was only visualized on [ 68 Ga]Ga-Pentixafor PET/CT images. Compared with [ 18 F]FDG, [ 68 Ga]Ga-Pentixafor PET/CT provided a 42% detection rate. Regarding semi-quantitative measures, the intensity of uptake and tumor-to-background ratios were significantly lower on [ 68 Ga]Ga-Pentixafor PET/CT [average maximum standard uptake value (SUV max ) of 2.72 ±â€…1.33 vs. 11.41 ±â€…14.79; P value <0.001 and 1.17 ±â€…0.53 vs. 5.32 ±â€…7.34; P value <0.001, respectively]. CONCLUSION: When comparing [ 68 Ga]Ga-Pentixafor PET/CT with [ 18 F]FDG PET/CT, not only did [ 68 Ga]Ga-Pentixafor PET/CT detect fewer lesions, but the intensity of uptake and the TBRs were also lower on [ 68 Ga]Ga-Pentixafor PET/CT. Thus, our results may indicate a limited potential of this novel tracer in cutaneous melanoma patients compared to [ 18 F]FDG PET/CT. Given the lower TBRs, applying this radiotracer in radioligand therapies is also questionable.

Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial.

BACKGROUND: Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI). METHODS: As a randomized clinical trial, one hundred twenty patients (103 male and 17 female) with angiographically confirmed CAD who were on long-term beta blocker therapy (≥3 months) enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60) in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60) without discontinuation of beta-blockers prior to DMPI. RESULTS: No significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility) in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096). Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001); however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898). The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7%) was not statistically different from group B (90%). CONCLUSION: Beta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.

Internal dosimetry of 64Cu-DOX-loaded microcapsules by Monte Carlo method.

Some of the issues regarding introducing new radiocompounds in nuclear medicine are the distribution patterns, delivered dose to different organs, diagnostic abilities and side effects. In this study, in order to assess the biodistribution of 64Cu-DOX-loaded microcapsules, rats were IV-injected with the microcapsules, and 1, 4, 14, and 24 h later, the activities of the targeted organs were measured (%ID/g). The accumulated activities were achieved by %ID/g curves, and S-factors were obtained by MCNP outputs. The MIRD formulation and Monte Carlo method were used to determine the absorbed dose in the target organs. The biodistribution data and PET-CT images showed that the lungs were where the majority of activity was seen. According to MIRD and MCNP, the maximum dose delivered in the lungs was 5.79E+01 mGy/MBq and 4.70E+01 mGy/MBq, respectively. Also, the effective dose was 1.2E+01 for MIRD and 8.31E+00 mSv/MBq for MCNP. These results indicate that 64Cu-DOX microcapsules can be considered a new radiocompound in pulmonary imaging, and MCNP simulation can be a reliable method for internal dosimetry.

Diagnostic value of [ 68 Ga]Ga-Pentixafor versus [ 18 F]FDG PET/CTs in non-small cell lung cancer: a head-to-head comparative study.

OBJECTIVE: In this study, we aimed to compare the diagnostic value of [ 68 Ga]Ga-Pentixafor and [ 18 F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients. METHODS: Patients with pathology-proven NSCLC were prospectively included. Patients underwent [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P -value <0.05 was considered significant. RESULTS: Twelve consecutive NSCLC patients (mean age: 60 ±â€…7) were included. All patients underwent both [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [ 68 Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [ 18 F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [ 18 F]FDG PET/CT ( P -values <0.05). Regarding the advantages, [ 68 Ga]Ga-Pentixafor depicted two brain metastases that were missed by [ 18 F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [ 18 F]FDG PET/CT scan was correctly classified as benign by subsequent [ 68 Ga]Ga-Pentixafor PET/CT. CONCLUSION: [ 68 Ga]Ga-Pentixafor PET/CT was concordant with [ 18 F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [ 18 F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [ 18 F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.

The influence of resolution recovery by using collimator detector response during 3D OSEM image reconstruction on (99m)Tc-ECD brain SPET images.

Partial volume effect, due to the poor spatial resolution of single photon emission tomography (SPET), significantly restricts the absolute quantification of the regional brain uptake and limits the accuracy of the absolute measurement of blood flow. In this study the importance of compensation for the collimator-detector response (CDR) in the technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) brain SPET was assessed, by incorporating system response in the ordered-subsets expectation maximization (OSEM) reconstruction algorithm. By placing a point source of (99m)Tc at different distances from the face of the collimator, CDR were found and modeled using Gaussian functions. A fillable slice of the brain phantom was designed and filled by (99m)Tc. Projections acquired from the phantom and also 4 patients who underwent the (99m)Tc-ECD brain SPET were used in this study. To reconstruct the images, 3D OSEM algorithm was used. System blurring functions were modeled, during the reconstruction in both projection and backprojection steps. Our results were compared with the conventional resolution recovery using Metz filter in filtered backprojection (FBP). Visual inspection of the images was performed by six nuclear medicine specialists. Quantitative analysis was also studied by calculating the contrast and the count density of the reconstructed images. For the phantom images, background counts and noise were decreased by 3D OSEM compared to the FBP-Metz method. Quantitatively, the ratio of the counts of the occupied hot region to that of the cold region of the reconstructed by FBP-Metz images was 1.14. This value was decreased from 1.12 to 0.86 for 3D OSEM of 2 and 30 iterations respectively. The reference value was 0.85 for the planar image. For clinical images, hot to cold regions (grey to white matter), the count ratio was increased from 1.44 in FBP-Metz to 3.2 and 4 in 3D OSEM with 10 and 20 iterations respectively. Based on the interpretability of images, the best scores (3.79±0.51) by the physicians were given to the images reconstructed by 3D OSEM and 10 iterations. This value was 0.63±0.77 for FBP-Metz images. In conclusion, by incorporating the distance dependent CDR during 3D OSEM, it was possible to reconstruct the brain images with much higher resolution and contrast as compared to the conventional resolution recovery method, which used FBP-Metz. It was however important to make a trade-off between noise and resolution by determining an optimum iterations number.

Prospective evaluation of technetium-99m ECD SPET in mild traumatic brain injury for the prediction of sustained neuropsychological sequels.

Our aim was to evaluate whether single photon emission tomography (SPET) versus computed tomography (CT) in acute phase of mild traumatic brain injury (MTBI) was better for the prediction of sustained neuropsychological symptoms beyond a typical recovery period. Forty five patients with MTBI were prospectively evaluated with clinical and neuropsychological exams, structural imaging using CT and perfusion study by(99m)Tc-ethylene cysteinate dimer ((99m)Tc-ECD) SPET within a week of the head trauma. After an interval ranging from 6 to 12 (median: 9) months, all patients were re-evaluated by standard neuropsychological tests for the assessment of sustained personality changes, imbalance and memory deficits. Our results showed that, 25 patients had abnormal brain perfusion on (99m)Tc-ECD SPET. In 19 cases of total 20 normal (99m)Tc-ECD SPET studies, no sign of memory deficit and imbalance was observed. Negative predictive value (NPV) for both complications was 95%. NPV of CT for the prediction of memory deficit and imbalance were 77.4% and 90.3%, respectively. The risk of developing sustained memory deficits and imbalance in patients with positive (99m)Tc-ECD SPET were 40% and 20%, respectively. A perfusion abnormality on (99m)Tc-ECD SPET was associated with a greater chance of long-standing memory deficits (odds ratio=13.49, P=0.020)while neither CT nor (99m)Tc-ECD SPET could independently predict the personality changes in these patients. The patients with abnormalities on both CT and SPET images faced a significant relative risk of complications, 1.63 times, higher than the others. In conclusion, our study indicated that (99m)Tc-ECD SPET imaging or CT imaging alone, could not predict the occurrence of sustained complications after MTBI. Concurrent use of both imaging modalities performed shortly after MTBI may yield the best results, as the combination of abnormalities in both cerebral structure and perfusion could indicate the patients with 1.63 times higher risk of sustained memory deficits, personality changes and imbalance.

99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer.

BACKGROUND: 99mTc-prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. PATIENTS AND METHODS: Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15-20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. RESULTS: In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0-5), whereas 43 (median of 2 regions per patient; range, 0-5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. CONCLUSIONS: 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern.

A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: [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.

The additive value of transient left ventricular dilation using two-day dipyridamole 99mTc-MIBI SPET for screening coronary artery disease in patients with otherwise normal myocardial perfusion: a comparison between diabetic and non-diabetic cases.

The prognostic value of transient ischemic dilation (TID) has been previously confirmed; however, its clinical significance for screening coronary artery disease (CAD) with balanced ischemia, as a cause of false negative myocardial perfusion imaging (MPI), is unclear. The goal of this study was to determine the additive diagnostic value of TID ratio for screening CAD in separate subgroups of diabetic and non-diabetics with normal perfusion. Eighty six patients with intermediate probability of CAD who had TID more than one in the presence of otherwise normal MPI using two-day technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) single photon emission tomography (SPET) and dipyridamole stress (summed stress score<3 and left ventricular cavity<90 mL) were included in a prospective cohort study comprising two subgroups of diabetic and non- diabetic patients. An inclusive work-up with multiple noninvasive tests was performed for all patients from whom 38 cases subsequently underwent coronary angiography and 48 cases were categorized in the group with a very low likelihood (<5%) of CAD on the basis of clinical and paraclinical data over a minimum of 18 months follow up. The TID ratio was calculated using automated software. Gensini score (GS) as an indicator of severity/extent of stenosis and coronary artery index (CAI) as the number of arteries with more than 50% narrowing were calculated based on angiographic findings. Our results showed that only in diabetic patients with three-vessel disease, TID ratio (1.47 ± 0.23) differs significantly from the other groups of CAD. In diabetic patients subgroup, TID ratio correlated strongly with GS (r=0.957, P<0.0001) and CAI (r=0.659, P=0.001), while such correlations were not seen in the non-diabetic patients. On the basis of receiver operating characteristic curve analysis for screening CAD in diabetic patients with normal myocardial perfusion, 100% sensitivity and 77.8% normalcy rate were achieved when TID more than 1.16 was regarded as abnormal. No distinct cut-off value for abnormal TID was obtained in the non-diabetic patients. In conclusion, TID in diabetic patients without regional myocardial perfusion abnormality is an important sign of CAD especially when TID ratio exceeds 1.16. The higher TID ratio in these cases may predict increasing possibility of severe and extensive CAD. The value of TID in non-diabetic patients with otherwise normal MPI is not clearly determined.