The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT.
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ABSTRACT:
SUBMITTER: Bouchard A
PROVIDER: S-EPMC8699502 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sentinel lymph node biopsy has been proposed as an alternative to up-front elective neck dissection (END) for determination of pathologic nodal status in patients undergoing surgical treatment for oral cavity squamous cell carcinoma (OSCC) with clinically negative neck (cN0). Sentinel lymph node biopsy using current standard tracer agents and imaging adjuncts such as radiolabeled sulfur-colloid and planar lymphoscintigraphy (LS), however, is associated with several drawbacks.To assess the preliminary utility of technetium Tc 99m (99mTc)-tilmanocept, a novel molecular imaging agent for sentinel lymph node (SLN) mapping, in OSCC.Prospective, nonrandomized, single-arm, part of an ongoing phase 3 clinical trial. Patients had previously untreated, clinically and radiographically node-negative OSCC (T1-4aN0M0) at an academic tertiary referral center.Patients received a single dose of 50 µg 99mTc-tilmanocept injected peritumorally followed by dynamic planar LS and fused single-photon emission computed tomography/computed tomography (SPECT/CT) prior to surgery. Surgical intervention consisted of excision of the primary tumor and radioguided SLN dissection followed by planned END. The excised lymph nodes (SLNs and non-SLNs) underwent histopathologic evaluation for presence of metastatic disease.False-negative rate and negative predictive value of SLNB using 99mTc-tilmanocept and comparison of planar LS with SPECT/CT in SLN localization.Twelve of 20 patients (60%) had metastatic neck disease on pathologic examination. All 12 had at least 1 SLN positive for metastases. No patients had a positive END node who did not have at least 1 positive SLN. These data yield a false-negative rate of 0% and negative predictive value of 100% using 99mTc-tilmanocept in this setting. Dynamic planar LS and SPECT/CT revealed a mean (range) number of hot spots per patient of 2.9 (1-7) and 3.7 (1-12), respectively. Compared with planar LS, SPECT/CT identified additional putative SLNs in 11 of 20 cases (55%).The high negative predictive value and low false-negative rate in identification of occult metastases shows 99mTc-tilmanocept to be a promising agent in SLN identification in patients with OSCC. Use of SPECT/CT improves preoperative SLN localization including delineation of SLN locations near the primary tumor when compared with planar LS imaging.clinicaltrials.gov Identifier: NCT00911326.
| S-EPMC4301415 | biostudies-literature
Project description:Extradomain-B fibronectin (EDB-FN), an oncofetal isoform of FN, is a promising diagnostic and therapeutic target of tumors, including breast cancer. Many EDB-FN-targeted drugs have been developed and have shown therapeutic effects in clinical trials. Molecular imaging to visualize EDB-FN-positive cancers may help select the right patients who will be benefit from EDB-FN-targeted therapy. Although a few EDB-FN-targeted imaging probes have been developed, the complicated manufacturing procedure and expensive material and equipment required limit their application for large-scale screening of EDB-FN-positive cancer patients. Thus, more simple and economic EDB-FN-targeted imaging probes are still urgently needed. Previously, we have identified a breast cancer-targeted peptide, CTVRTSADC. Coincidently, it was later identified as an EDB-FN-targeted peptide and named ZD2. In this study, we found a positive correlation between the binding activity of the ZD2 phage and the expression level of EDB-FN in breast cancer cells. Moreover, we observed the colocalization of the ZD2 peptide with EDB-FN in breast cancer cells. Furthermore, in vivo tumor targeting of the ZD2 phage, near-infrared fluorescence imaging, and flow cytometry showed tumor-specific homing of the ZD2 peptide in mice bearing EDB-FN-positive breast cancers. Importantly, on the basis of this EDB-FN-targeted ZD2 peptide, we developed a kit-formulated probe, 99mTc-HYNIC-ZD2, for single-photon-emission computed tomography (SPECT) imaging of breast cancer. The high tumor uptake of 99mTc-HYNIC-ZD2 demonstrated its feasibility for use in visualizing EDB-FN-positive breast cancers in vivo. This kit-formulated EDB-FN-targeted SPECT probe has potential clinical applications for precision screening of EDB-FN-positive cancer patients who may benefit from EDB-FN-targeted therapy.
| S-EPMC6044779 | biostudies-literature
Project description:A well-established approach for diagnostic imaging of osteomyelitis (OM), a bone infection, is simultaneous SPECT-CT of 99mTc sulfur colloid (SC) and 111In white blood cells (WBC). This method provides essentially perfect spatial registration of the tracers within anatomic sites of interest. Currently, diagnosis is based purely on a visual assessment-where relative discordance between 99mTc and 111In uptake in bone, i.e., high 111In and low 99mTc, suggests OM. To achieve more quantitative images, noise, scatter, and crosstalk between radionuclides must be addressed through reconstruction. Here the authors compare their Monte Carlo-based joint OSEM (MC-JOSEM) algorithm, which reconstructs both radionuclides simultaneously, to a more conventional triple-energy window-based reconstruction (TEW-OSEM), and to iterative reconstruction with no compensation for scatter (NC-OSEM).The authors created numerical phantoms of the foot and torso. Multiple bone-infection sites were modeled using high-count Monte Carlo simulation. Counts per voxel were then scaled to values appropriate for 111In WBC and 99mTc SC imaging. Ten independent noisy projection image sets were generated by drawing random Poisson deviates from these very low-noise images. Data were reconstructed using the two iterative scatter-compensation methods, TEW-OSEM and MC-JOSEM, as well as the uncorrected method (NC-OSEM). Mean counts in volumes of interest (VOIs) were used to evaluate the bias and precision of each method. Data were also acquired using a phantom, approximately the size of an adult ankle, consisting of regions representing infected and normal bone marrow, within a bone-like attenuator and surrounding soft tissue; each compartment contained a mixture of 111In and 99mTc. Low-noise data were acquired during multiple short scans over 29 h on a Siemens Symbia T6 SPECT-CT with medium-energy collimators. Pure 99mTc and 111In projection datasets were derived by fitting the acquired projections to the sum of 99mTc and 111In contributions, using the known half-lives. Uncontaminated data were scaled and recombined into six datasets with different activity ratios; ten Poisson noise realizations were then generated for each ratio. VOIs in each of the compartments were used to evaluate the bias and precision of each method with respect to reconstructions of uncontaminated datasets. In addition to the simulated and acquired phantom images, the authors reconstructed patient images with MC-JOSEM and TEW-OSEM. Patient reconstructions were assessed qualitatively for lesion contrast, spatial definition, and scatter.For all simulated and acquired infection phantoms, the root-mean squared-error of measured 99mTc activity was significantly improved with MC-JOSEM and TEW-OSEM in comparison to NC-OSEM reconstructions. While MC-JOSEM trended toward outperforming TEW-OSEM, the improvement was only found to be significant (p<0.001) for the acquired bone phantom in which a wide range of 111In∕99mTc concentration ratios were tested. In all cases, scatter correction did not significantly improve 111In quantitation.Compensation for scatter and crosstalk is useful for improving quality, bias, and precision of 99mTc activity estimates in simultaneous dual-radionuclide imaging of OM. The use of the more rigorous MC-based estimates provided marginal improvements over TEW. While the phantom results were encouraging, more subjects are needed to evaluate the usefulness of quantitative 111In∕99mTc SPECT-CT in the clinic.
| S-EPMC3716783 | biostudies-other
Project description:BACKGROUND:Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs). METHODS:Dual-gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. RESULTS:The estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (?IMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ?IMBV. Estimates of IMBV and ?IMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 ? 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. CONCLUSIONS:Non-invasive quantification of IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.
| S-EPMC5985225 | biostudies-literature
Project description:Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the basal ganglia. Single photon emission computed tomography (SPECT) scans using [99mTc]TRODAT-1 can image dopamine transporters and provide valuable diagnostic information of PD. In this study, we optimized the scanning parameters for [99mTc]TRODAT-1/SPECT using the Taguchi analysis to improve image quality. SPECT scans were performed on forty-five healthy volunteers according to an L9 orthogonal array. Three parameters were considered, including the injection activity, uptake duration, and acquisition time per projection. The signal-to-noise ratio (SNR) was calculated from the striatum/occipital activity ratio as an image quality index. Ten healthy subjects and fifteen PD patients were used to verify the optimal parameters. The estimated optimal parameters were 962 MBq for [99mTc]TRODAT-1 injection, 260 min for uptake duration, and 60 s/projection for data acquisition. The uptake duration and time per projection were the two dominant factors which had an F-value of 18.638 (38%) and 25.933 (53%), respectively. Strong cross interactions existed between the injection activity/uptake duration and injection activity/time per projection. Therefore, under the consideration of as low as reasonably achievable (ALARA) for radiation protection, we can decrease the injection activity to 740 MBq. The image quality remains almost the same for clinical applications.
| S-EPMC4366084 | biostudies-literature
Project description:99mTc-iminodiacetic acid (IDA) hepatobiliary imaging is usually quantified for hepatic function on the entire liver or regions of interest (ROIs) in the liver. The authors presented a method to estimate the hepatic extraction fraction (HEF) voxel-by-voxel from single-photon emission computed tomography (SPECT)∕CT with a 99mTc-labeled IDA agent of mebrofenin and evaluated the spatially resolved HEF measurements with an independent physiological measurement.Fourteen patients with intrahepatic cancers were treated with radiation therapy (RT) and imaged by 99mTc-mebrofenin SPECT before and 1 month after RT. The dynamic SPECT volumes were with a resolution of 3.9 × 3.9 × 2.5 mm(3). Throughout the whole liver with approximate 50 000 voxels, voxelwise HEF quantifications were estimated and compared between using arterial input function (AIF) from the heart and using vascular input function (VIF) from the spleen. The correlation between mean of the HEFs over the nontumor liver tissue and the overall liver function measured by Indocyanine green clearance half-time (T1∕2) was assessed. Variation of the voxelwise estimation was evaluated in ROIs drawn in relatively homogeneous regions of the livers. The authors also examined effects of the time range parameter on the voxelwise HEF quantification.Mean of the HEFs over the liver estimated using AIF significantly correlated with the physiological measurement T1∕2 (r = 0.52, p = 0.0004), and the correlation was greatly improved by using VIF (r = 0.79, p < 0.0001). The parameter of time range for the retention phase did not lead to a significant difference in the means of the HEFs in the ROIs. Using VIF and a retention phase time range of 7-30 min, the relative variation of the voxelwise HEF in the ROIs was 10% ± 6% of respective mean HEF.The voxelwise HEF derived from 99mTc-IDA SPECT by the deconvolution analysis is feasible to assess the spatial distribution of hepatic function in the liver.
| S-EPMC3751955 | biostudies-other
Project description:PurposeThe differentiation of oncocytoma from renal cell carcinoma (RCC) remains a challenge with currently available cross-sectional imaging techniques. As a result, a large number of patients harboring a benign oncocytoma undergo unnecessary surgical resection. In this study, we explored the utility of 99mTc-MIBI SPECT/CT for the differentiation of these tumors based on the hypothesis that the large number of mitochondria in oncocytomas would lead to increased 99mTc-MIBI uptake.Patients and methodsIn total, 6 patients (3 with oncocytoma and 3 with RCC) were imaged with 99mTc-MIBI SPECT/CT. Relative quantification was performed by measuring tumor-to-normal renal parenchyma background ratios.ResultsAll 3 oncocytomas demonstrated radiotracer uptake near or above the normal renal parenchymal uptake (range of uptake ratios, 0.85-1.78). In contrast, the 3 RCCs were profoundly photopenic relative to renal background (range of uptake ratios, 0.21-0.31).Conclusions99mTc-MIBI SPECT/CT appears to be of value in scintigraphically distinguishing benign renal oncocytoma from RCC.
| S-EPMC4358706 | biostudies-literature
Project description:Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation). However, despite their great success in the clinic, a significant number of patients do not respond to EGFR-TKIs, such as those carrying the L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we report a novel SPECT tracer 99mTc-HYNIC-MPG that binds specifically to activating mutant EGFR and which could therefore be used to noninvasively select patients sensitive to EGFR-TKIs. We evaluated the capacity of 99mTc-HYNIC-MPG in detecting EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell lines (PC9, H1975, H358 and H520). 99mTc-HYNIC-MPG had significantly higher accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors cells, which may be due to the activating mutations (exon 19 deletion) in EGFR tyrosine kinase domain in PC9 cells. Thus, 99mTc-HYNIC-MPG SPECT imaging may be used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs.
| S-EPMC5522229 | biostudies-literature
Project description:Although pathological confirmation is the gold standard for diagnosis of amyloidosis, there is a need for a relevant imaging modality to identify involved organs and evaluate disease extent. Thus, we prospectively investigated imaging findings of Tc-DPD scintigraphy in AL and ATTR amyloidosis.A total of 21 subjects with pathologically confirmed AL or ATTR amyloidosis were included. Pretreatment whole body Tc-DPD planar scanning and regional SPECT/CT were performed in all subjects. For allegedly involved organs, Tc-DPD uptake was visually and semi-quantitatively evaluated on a 4-point scale (grade 0: no uptake, 1: uptake less than spine, 2: uptake similar to spine, and 3: uptake greater than spine).There were 29 organs involved in AL and 12 in ATTR. Significant Tc-DPD uptake was found in 24 organs (sensitivity?=?82.8%) in AL and 9 organs (sensitivity?=?75.0%) in ATTR. Additional SPECT/CT was helpful to ensure abnormal DPD uptake in the involved organs, which was uncertain by attenuation in planar imaging. Degree of Tc-DPD uptake was significantly higher in ATTR compared with AL amyloidosis (P?=?.017). Diffuse soft tissue uptake with photon defects in the liver area was found only in ATTR amyloidosis.This study showed that Tc-DPD scintigraphy might have capacity to differentiate between AL and ATTR subtypes with good sensitivity in various organs involving primary systemic AL and ATTR amyloidosis. Additional SPECT/CT significantly improved the diagnostic efficacy of Tc-DPD scintigraphy.
| S-EPMC7004596 | biostudies-literature
Project description:Using conventional imaging modalities, it is difficult to detect recurrent lesions in prostate cancer patients who have undergone biochemical relapse, especially in patients with low prostate-specific antigen (PSA) levels. We retrospectively reviewed the files of fifty patients with histopathologically confirmed prostate cancer who underwent 99mTc-labeled prostate-specific membrane antigen (PSMA) single-photon emission computed tomography (SPECT)/computed tomography (CT), magnetic resonance imaging (MRI), and bone scan within a 30-day period. PSMA-SPECT/CT indicated metastatic lesions in 39 patients and had a higher detection rate (78.0%) than bone scan (34.0%) or MRI (40.0%). The diagnostic efficiency of PSMA-SPECT/CT imaging for bone and lymph node metastases (50.0% and 42.0%) was better than bone scan (34.0% and 0.0%) or MRI (24.0% and 20.0%). PSMA-SPECT/CT provided a higher detection rate at serum PSA levels of ≤1 ng ml-1, 1-4 ng ml-1, 4-10 ng ml-1, and >10 ng ml-1. No correlation was found between Gleason score, PSA level, and the tracer tumor/background ratio of metastatic lesions. With the aid of PSMA-SPECT/CT imaging, the therapeutic strategy was changed for 31 patients, and this may have enhanced their clinical outcome. In conclusion, PSMA-SPECT/CT imaging could detect more metastatic lesions and achieve a higher detection rate than conventional imaging modalities at different serum PSA levels in prostate cancer patients who had undergone biochemical relapse.
| S-EPMC5427779 | biostudies-literature