ABSTRACT
ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.
ABSTRACT
Aims: This study aimed to investigate the effect of gallium nitrate [Ga(NO3)3], an inorganic antimicrobial agent, against the growth and biofilm formation of Staphylococcus aureus on the titanium surface. Study Design: This study is a laboratory investigation involving the determination of the inhibitory concentration (IC) of Ga(NO3) 3 against the planktonic strain of S. aureus and biofilm formation on titanium coupons. Place and Duration of Study: Sample: Center of Science and Technology for Sustainability (CCTS), Federal University of São Carlos, SP, Brazil, between March 2020 and March 2022. Methodology: The inhibitory concentration of gallium nitrate was determined in a 96-well microtiter plate in Muller Hinton broth. The potential of the antimicrobial agent to inhibit biofilm formation by S. aureus on titanium surfaces was evaluated by Scanning Electron Microscopy (SEM). The cytotoxicity potential of Ga(NO3)3 was determined on V79 cells. Results: The results showed that the susceptibility of gallium nitrate against S. aureus was 1.40 µM, while SEM images revealed that concentrations of 90 µM inhibited biofilm formation by S. aureus. Conclusion: This research has shown promising results regarding gallium nitrate's potential of inhibiting the growth of both planktonic and sessile S. aureus cells. In addition, coating titanium surfaces with Ga(NO3)3 would be an extra alternative to prevent implant-associated infections due to its non-toxicity to cells.
ABSTRACT
Abstract Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in normal prostate cells and overexpressed in prostate cancer. Consequently, it is an important tool in the evaluation of prostate cancer, including the staging of high-risk patients and the assessment of biochemical recurrence. Despite the "specific" designation, benign musculoskeletal conditions, such as fractures, osteodegenerative changes, and fibrous dysplasia, can also show PSMA uptake, which can lead to misinterpretation of the imaging findings. Therefore, radiologists must be aware of these potential pitfalls, understand their causes, and fully analyze their morphologic features on unfused computed tomography (CT) and magnetic resonance imaging scans to correctly interpret the examination. In this pictorial essay, we review the basic characteristics of the 68Ga-PSMA positron-emission tomography/CT (PET/CT) radiotracer, discuss potential causes of false-positive findings on 68Ga-PSMA PET/CT in the musculoskeletal system, and illustrate the corresponding imaging findings.
Resumo O antígeno de membrana próstata específico (PSMA) é uma proteína transmembrana que apresenta expressão em células prostáticas normais e superexpressão em neoplasia da próstata. Dessa forma, é uma importante ferramenta na avaliação da neoplasia prostática, de utilidade no estadiamento de pacientes de alto risco e na análise de recorrência bioquímica. Apesar do termo "específico", condições musculoesqueléticas benignas podem demonstrar captação de PSMA, como fraturas, alterações osteodegenerativas e displasia fibrosa, podendo levar a uma avaliação equivocada dos achados de imagem. Assim, o radiologista deve conhecer esses potenciais pitfalls, compreender suas causas e analisar as características morfológicas nas imagens não fundidas de TC e RM para interpretar corretamente o exame. Neste ensaio iconográfico, revisaremos as características básicas do radiofármaco 68Ga-PSMA PET/CT, discutiremos possíveis causas de resultados falso-positivos na 68Ga-PSMA PET/CT no sistema musculoesquelético e ilustraremos os achados de imagem correspondentes.
ABSTRACT
Abstract Objective: To determine the diagnostic accuracy of Necrotizing Otitis Externa (NOE) based on radiologic studies. Methods: The PubMed, Cochrane, Embase, Web of Science, SCOPUS, and Google Scholar databases were searched. True-positive and false-negative results were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results: The included studies contained data on 37 studies diagnosed with NOE. The sensitivity of gallium-67, technetium-99m, and Magnetic Resonance Imaging (MRI) was 0.9378 (0.7688-0.9856), 0.9699 (0.8839-0.9927), and 0.9417 (0.6968-0.9913), respectively. For Computed Tomography (CT), the positive criteria consisted of bony erosion alone and bony erosion plus any soft tissue abnormality. The sensitivity of CT based only on bony erosion was 0.7062 (0.5954-0.7971); it was higher 0.9572 (0.9000-0.9823) when based on bony erosion plus any soft tissue abnormality. Conclusion: The diagnostic sensitivity of technetium-99m, gallium-67, and MRI was favorable. On CT, the presence of bony erosion may be a useful diagnostic marker of NOE, but the diagnostic sensitivity will be even higher if the criterion of any soft tissue abnormality is also included; however, care should be taken when interpreting the results. Our study demonstrates the potential utility of radiology studies for diagnosing NOE, but their lack of specificity must be considered, and standardized anatomic criteria are still needed. Level of evidence: 2A.
ABSTRACT
Objective Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (68Ga-FAPI PET). Methods We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and 68Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients. Results A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high 68Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake. Conclusions FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.
ABSTRACT
Objective:To produce 68Ga and automatically synthesize 68Ga-labeled drugs based on low-energy medical cyclotron solid target system. Methods:68Zn was electroplated on the surface of the target by electrodeposition. According to the principle of 68Zn(p, n) 68Ga nuclear reaction, 68Zn was irradiated by the 10 MeV medical cyclotron solid target system (30 μA, 30 min) to produce 68Ga, and the activity, nuclear purity, half-life and content of metal impurities of purified product were determined. 68Ga-prostate specific membrane antigen (PSMA)-11 and 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) were synthesized automatically using 68Ga respectively, and the quality control analyses of drug properties, concentration, pH, radiochemical purity, sterility and bacterial endotoxin were carried out. Results:The electroplating mass of 68Zn was (43.71±0.87) mg ( n=35), the yield of 68Ga after irradiation was (10.96±0.67) GBq ( n=35), and the measured half-life was (67.64±0.06) min ( n=7). Only 511 keV energy peak was detected by the gamma spectrometer. After purification, (6.85±0.12) GBq ( n=35) of pure 68Ga was obtained, and the purification efficiency was (62.46±0.96)% (non-attenuated correction, n=35). The metal impurity contents of Zn and Fe were (0.18±0.06) and (1.25±0.43) μg/GBq ( n=5), which met the requirements of European Pharmacopoeia. Three batches of 68Ga-PSMA-11 and 68Ga-DOTATATE were automatically synthesized, with the yield, concentration and radiochemical purity of (3.54±0.14) and (2.74±0.20) GBq, (294.97±11.58) and (228.17±16.32) GBq/L, (99.73±0.11)% and (99.45±0.25)%, respectively. Both sterility and bacterial endotoxin were qualified. Conclusion:High-yield and qualified nuclide 68Ga and 68Ga-labeled drugs are successfully prepared through the low-energy medical cyclotron solid target system and the automated purification and synthesis module, which provide a strong guarantee for clinical practice.
ABSTRACT
Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.
ABSTRACT
Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.
ABSTRACT
Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.
ABSTRACT
Objective:To explore the value of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in newly diagnosed prostate cancer patients with different risk stratifications, and to compare the performance of this modality with conventional imaging in detecting metastases. Methods:From June 2019 to July 2020, the clinical and imaging data of 60 patients (age range: 44-88 years, median age 69 years) who underwent 68Ga-PSMA-11 PET/CT imaging in Fudan University Shanghai Cancer Center were retrospectively analyzed. Spearman rank correlation analysis was used to explore the correlation of SUV max in primary foci with prostate specific antigen (PSA) and Gleason score (GS). Based on the D′Amico risk stratification (PSA>20 μg/L and ≤20 μg/L, GS>7 and ≤7), the detection rates of 68Ga-PSMA-11 PET/CT for metastases were evaluated by χ2 test, and the differences of SUV max were analyzed by Mann-Whitney U test. Patients were divided into high-risk (PSA>20 μg/L and GS>7), medium-risk (PSA>20 μg/L and GS≤7, or PSA≤20 μg/L and GS>7), and low-risk (PSA<20 μg/L and GS<7) groups according to PSA levels and GS. Compared with conventional imaging (bone imaging, CT or MRI), the ability of 68Ga-PSMA-11 PET/CT to detect metastatic tumors, and the utility to change the prostate cancer stage were evaluated by Fisher′s exact test. Results:High uptake of 68Ga-PSMA-11 was observed in primary lesions of 60 patients, and SUV max was positively correlated with GS or PSA ( rs values: 0.42, 0.38; P values: 0.001, 0.002). The detection rates of lymph node and bone metastases in the group with PSA>20 μg/L were 11/18 and 13/18, respectively, which were higher than those in the group with PSA≤20 μg/L (28.57%(12/42) and 35.71%(15/42); χ2 values: 6.56, 7.56, P values: 0.010, 0.006. However, there was no statistical significance in the SUV max of these lesions( z values: -1.04, -0.96; P values: 0.299, 0.337). There was a statistical difference in the detection rates of lymph node and bone metastases between the group with GS>7 and the group with GS≤7 (lymph node: 54.05%(20/37) vs 13.04%(3/23), χ2=10.09, P=0.001; bone metastases: 59.46%(22/37) vs 26.09%(6/23), χ2=8.19, P=0.004), as well as the SUV max of bone metastases( z=-2.02, P=0.044). In the high-risk group, 68Ga-PSMA-11 PET/CT had the higher detection rate of metastases than conventional imaging (16/17 vs 10/17; P=0.039) and it changed 25.0%(15/60) of the patients′ staging. Conclusions:PSA and GS affect the detection rate of 68Ga-PSMA-11 PET/CT. In patients with high-risk prostate cancer, 68Ga-PSMA-11 PET/CT is superior to conventional imaging in detecting metastases. When PSA>20 μg/L and GS>7, it is better to use 68Ga-PSMA-11 PET/CT in prostate cancer staging.
ABSTRACT
Abstract Temporomandibular joint dysfunction syndrome (TMD), is a collective term characterized by symptoms involving chewing muscles, temporomandibular joint and orofacial structures. The efficacy of low intensity laser (LLLT) Gallium arsenide, in combination with a non-steroidal anti-inflammatory drug (NSAID) was evaluated. The main objective was to evaluate the maximum mouth opening without pain (ABM), arthralgia in the joint capsule through visual analog scale (VAS), laterality, protrusion, joint noises and count of tablets ingested per group. A controlled clinical trial (double-blind-randomized) was carried out in 30 subjects, who presented DTM of arthrogenic etiology; 5 applications of LLLT were made with wavelength of 810 nm, output optical power of 100-200 mw, emission PW=Pulsed (1-10,000Hz), dose of 10 jouls-cm², time of 1.44 minutes in mouth closed and with the mouth half open. One more follow-up appointment per month. There were two groups: experimental and control group, where different variables were analyzed (ABM, laterality, protrusion, VAS and sociodemographic). In the control group, a supposed LT application (not active) was made, for later comparison. Pain-free ABM was assessed in all appointments in addition to the other clinical parameters. Repeated measures analysis was performed with mixed models. Thirty patients were included of which 28 finished the treatment, two of them were lost during follow-up. The groups were similar in all their baseline variables. There were no statistically significant differences when applying the final multiple regression analysis, in the ABM, or in any other of the clinical parameters analyzed. LT was not effective in treating arthrogenic DTM.
Resumen El síndrome de disfunción de la articulación temporomandibular (DTM) es un término colectivo caracterizado por síntomas que involucran músculos de la masticación, articulación temporomandibular y estructuras orofaciales. Se evaluó la eficacia del láser de baja intensidad (LLLT) Arseniuro de galio, en combinación con un antiinflamatorio no esteroideo (AINE). El objetivo principal fue evaluar la apertura bucal máxima sin dolor (ABM), la artralgia en cápsula articular a través de escala visual análoga (EVA), lateralidades, protrusión, ruidos articulares y conteo de tabletas ingeridas por grupo. Se realizó un ensayo clínico controlado (doble ciego-aleatorizado) en 30 sujetos, que presentaban DTM de etiología artrogénica; se les realizaron 5 aplicaciones de LLLT con longitud de onda de 810 nm, potencia óptica de salida de 100-200 mw, emisión PW=Pulsed (1-10,000Hz), dosis de10 jouls-cm², tiempo de1.44 minutos a boca cerrada y con la boca semiabierta. Una cita más de seguimiento al mes. Se tuvieron dos grupos: experimental y grupo control, donde se analizaron diferentes variables (ABM, lateralidades, protrusión, EVA y sociodemográficas). En el grupo control se hizo una supuesta aplicación LT (no activo), para posterior comparación. En todas las citas se valoró la ABM sin dolor además de los otros parámetros clínicos. Se realizó análisis de medidas repetidas con modelos mixtos. Se incluyeron 30 pacientes de los cuales 28 finalizaron el tratamiento, dos de ellos se perdieron en el seguimiento. Los grupos fueron similares en todas sus variables basales. No hubo diferencias estadísticas significativas al aplicar los análisis de regresión múltiple finales, en la ABM, ni tampoco en ningún otro de los parámetros clínicos analizados. El LT no fue eficaz en el tratamiento de la DTM de origen artrogénico.
Subject(s)
Humans , Temporomandibular Joint Dysfunction Syndrome , Low-Level Light Therapy/methods , Craniomandibular Disorders/therapyABSTRACT
Objective:To explore the relation of the radiochemical purity and in vivo imaging effect of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-phe1-Tyr3-Thr8-octreotide (TATE) injection. Methods:High performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) methods were established to determine 68Ga-DOTATATE, 68Ga 3+ , 68Ga in colloidal form and 68Ga-DOTA- D-Phe1-Tyr3-Thr8-dethreonine-octreotide (heptapeptide) and to study the influence of precursor purity on radiochemical purity of labelled products. The uptake of 68Ga-DOTATATE injection with different radiochemical purities was investigated in nude mice bearing AR42J cells by microPET imaging and the tumor target/non-target (T/NT) value was calculated. One-way analysis of variance and Pearson correlation analysis were used to analyze the data. Results:The contents of 68Ga 3+ and 68Ga in colloidal form were not related with precursor purity ( r values: 0.385, 0.497, P values: 0.306, 0.137), while the content of 68Ga-DOTA-heptapeptide was positively related with the purity of DOTA-heptapeptide ( r=0.957, P<0.001). The radiochemical purities of 68Ga-DOTATATE injection were (87.0±2.3)%, (86.8±0.8)% and (94.0±3.1)% when the DOTATATE purities were 90.9%, 91.6% and 99.2%, respectively. The results of microPET imaging showed that the tumor uptake was positively related with the radiochemical purity of 68Ga-DOTATATE injection ( r=0.828, P<0.001), and the T/NT values of 68Ga-DOTATATE injection with radiochemical purities of 95.7%, 85.8%, 84.5% and 79.9% were 21.25±8.84, 8.50±1.51, 11.38±1.65 and 6.01±0.99, respectively ( F=11.48, P=0.001). Conclusion:The radiochemical purity of 68Ga-DOTATATE injection is impacted by the purity of labelled precursor and manufacturing processes and is related with the imaging effect in vivo.
ABSTRACT
Objective:To explore the value of SPECT/CT imaging on programmed death receptor 1 ligand (PD-L1) expression in patients with non-small cell lung cancer (NSCLC) based on 99Tc m labeled anti-PD-L1 nanoantibodies (NM-01). Methods:From January 2019 to March 2020, a total of 14 patients (11 males, 3 females; age: (61.9±11.0) years) with pathologically confirmed NSCLC in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were prospectively enrolled. NM-01 were labeled with 99Tc m, and patients were recruited for SPECT/CT imaging 2 h after injection with 99Tc m-NM-01((359.1±68.0) MBq). The differences of SUV max in primary and metastatic lesions between PD-L1 positive and negative patients were compared by independent sample t test. The correlation between the SUV max and PD-L1 expression of primary lesions was analyzed by Pearson correlation analysis. Results:Of 14 patients, 6 were PD-L1 positive and 8 were PD-L1 negative. 99Tc m-NM-01 showed obviously increased uptake in kidneys and liver, while mildly increased uptake in spleen and bone marrow. The SUV max of primary lesions was 4.69±1.88 and the SUV max of metastatic lesions was 2.04±1.32. The SUV max of primary lesions in PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (5.99±1.99 vs 3.72±1.10; t=5.98, P=0.039). There was no significant difference in the SUV max of metastatic lesions between PD-L1 positive and negative patients (1.66±1.03 vs 2.35±1.46; t=-1.77, P=0.084). The SUV max of primary lesions was positively correlated with PD-L1 expression ( r=0.648, P=0.042). Conclusion:99Tc m-NM-01 can demonstrate the expression of PD-L1 in primary and metastatic lesions in NSCLC.
ABSTRACT
Objective:To explore the feasibility of pretargeting technique for immunoPET with epidermal growth factor receptor (EGFR) monoclonal antibody in EGFR positive/negative tumor bearing mice.Methods:Cetuximab- Trans-cyclooctene (TCO)was obtained by modifying Cetuximab with TCO- N-hydroxysuccinimide (NHS). 2, 2′-((6-amino-1-(4, 7-bis-(carboxymethyl)-1, 4, 7-triazonan-1-yl)hexan-2-yl)azanediyl)-diacetic acid (L-NETA)was used as a chelating agent to prepare the radioligand 68Ga-L-NETA-tetrazine (Tz), then the labeling rate and in vitro stability of the product were determined. Human basal breast cancer cells MDA-MB-468 (EGFR+ ) and MDA-MB-231 (EGFR-) were cultured in vitro. In vitro experiments were performed to explore the specificity of the probe and the feasibility of pretargeting technique. Nude mice (Balb/c-nu) bearing xenografts of the above two cell lines were established. Cetuximab-TCO (50 μg) was injected into the tumor-bearing mice in advance, then 68Ga-L-NETA-Tz was injected at different time points (48, 36, 24 and 12 h), and pretargeting was realized through " click chemistry" . Small-animal PET imaging and biodistribution were performed to evaluate pharmacokinetic properties and specificity of the probe. The one-way analysis of variance was used to compare the data. Results:The 68Ga-L-NETA-Tz molecular probe was successfully prepared with the labeling yield >95%, and the radiochemical purity was >95% after 2 h. Cetuximab-TCO and 68Ga-L-NETA-Tz were added to MDA-MB-468 cells successively, and the cell uptake rate reached (0.69±0.04)% at 1 h, which demonstrated the feasibility of the pretargeting technique. PET imaging and biodistribution results showed that the best imaging results were obtained in 36 h pre-injection group, in which the tumor uptake was the highest ((0.77±0.05) percentage activity of injection dose per gram of tissue (%ID/g), 1 h) and the tumor/muscle ratio was optimal (4.67±0.46); the tumor uptake in the blocking group, the group without injecting Cetuximab-TCO, and the MDA-MB-231 group were significantly lower ((0.35±0.01), (0.39±0.05), (0.45±0.10) %ID/g; F=15.50, P=0.002). Conclusions:EGFR targeted immunoPET imaging is successfully performed in mouse models of breast cancer by injecting Cetuximab-TCO and 68Ga-L-NETA-Tz successively. It provides an effective method for immunoPET imaging of monoclonal antibodies.
ABSTRACT
Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.
ABSTRACT
Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.
ABSTRACT
Objective:To evaluate the specificity of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Ser-Asn-Thr-Arg-Val-Ala-Pro (SNTRVAP, VAP) molecular probe targeting glucose-regulated protein 78(GRP78) in vivo and in vitro and the feasibility of 68Ga-DOTA-VAP microPET/CT imaging in the diagnosis of GRP78-positive tumors. Methods:68Ga-DOTA-VAP was prepared by the combination of bifunctional chelating agent DOTA and VAP, followed by 68Ga labeling. Western blotting experiment was perfomed to detect the expression of GRP78 in U87MG, BxPC-3, and 293T cell lines, at the same time, cold polypeptide blocked experiments were conducted to verify the specific binding of 68Ga-DOTA-VAP to cells. U87MG and BxPC-3 subcutaneous transplantation tumor mouse models were established and the biodistribution of 68Ga-DOTA-VAP were explored in vivo. The imaging effect of 68Ga-DOTA-VAP in GRP78-positive tumor-bearing mouse models was evaluated by microPET/CT. Independent-sample t test, one-way analysis of variance and Dunnett t test were used for data analysis. Results:68Ga-DOTA-VAP was easily prepared with labeling yield and radiochemical purity >98%. It had good stability in vitro, and its radiochemical purity was still (98.27±0.22)% after 2 h. GRP78 was highly expressed in U87MG and BxPC-3 cells, but lowly expressed in 293T cells ((0.78±0.02), (0.53±0.05) and (0.36±0.03), F=102.22, P<0.001; t values: 0.43, 0.18, both P<0.01). The uptake of 68Ga-DOTA-VAP in U87MG cells was higher than that in BxPC-3 cells (5 154.00±216.70 vs 4 344.00±60.88; t=3.10, P=0.027). Excessive unlabeled VAP polypeptide could significantly reduce the uptake of 68Ga-DOTA-VAP both in U87MG and BxPC-3 cells (3 324.00±54.14, 3 270.00±131.10; t values: 8.19, 7.43, both P<0.01). The uptake of 68Ga-DOTA-VAP in U87MG tumor tissue was higher than that in BxPC-3 tumor tissue ((1.98±0.20) vs (1.30±0.08) percentage activity of injection dose per gram of tissue (%ID/g); t=5.48, P=0.005), while co-injection of excessive unlabeled VAP polypeptide significantly reduced the uptake in U87MG and BxPC-3 tumors ((0.99±0.02) and (0.62±0.05) %ID/g; t values: 8.32, 12.25, both P<0.05). MicroPET/CT imaging showed that 68Ga-DOTA-VAP could clearly display U87MG and BxPC-3 tumors, and U87MG had a better imaging effect. The tumors could not be clearly visualized after co-injection of excessive VAP polypeptide. Conclusion:68Ga-DOTA-VAP molecular probe binds with GRP78 specifically and can reflect the expression level of GRP78 in vivo, which may be a promising probe for the specific imaging diagnosis of GRP78-positive tumors.
ABSTRACT
Objective:To compare the effect of different β values on the semi-quantitative accuracy and image quality of 68Ga-prostate specific membrane antigen (PSMA) PET/CT imaging after partial volume effect correction (PVC). Methods:In the model experiment, image reconstruction was carried out based on block sequential regularized expectation maximization algorithm (BSREMA) with the range of β values from 100 to 1 000. Recovery coefficient (RC), contrast recovery (CR) and background variability (BV) were measured to evaluate semi-quantitative accuracy and image quality. In the clinical study, image data of 21 prostate cancer patients (age 45-78 years) who underwent 68Ga-PSMA PET/CT examination in the First Hospital of Shanxi Medical University from March 2019 to February 2020 were retrospectively collected. A total of 29 abdominal imaging positive lymph nodes were divided into the small lymph node group (diameter <10 mm; n=12) and the large lymph node group (10 mm≤diameter≤30 mm; n=17). SUV parameters including SUV max, SUV mean and peak of SUV (SUV peak) and the influence of different β values on the SUV parameters were evaluated. The signal to noise ratio (SNR) and subjective scores were used to evaluate image quality. Independent-sample t test, Kappa test and Pearson correlation analysis were used to analyze data. Results:The model experiment showed that CR, RC and BV decreased with the increase of β values. The image quality, image clarity, lesion significance, and total image scores given by nuclear medicine physicians showed strong consistency ( Kappa values: 0.65-0.87, P values: 0.026-0.043). The small lymph node group had the highest score (13 and 14) with β value of 600, while the large lymph node group had the highest score (13 and 14) with β value of 700. SNR of the two groups increased steadily within β values from 100 to 600 ( t values: 2.49-8.99, P values: 0.023-0.038). When the β value was higher than 600, SNR of the small lymph node group reached a plateau ( t values: 1.28-2.00, P values: 0.072-0.098), while the SNR of the large lymph node group continued to increase ( t values: 2.98-4.63, P values: 0.012-0.029). Before PVC, there were significant negative correlations between SUV parameters and β values ( r values: from -0.94 to -0.64, P values: 0.039-0.046). After PVC, it was found that SUV mean and SUV max still had significant negative correlation with β values ( r values: from -0.78 to -0.68, P values: 0.035-0.042), while the SUV peak showed no significant correlation with β values ( r values: -0.22, -0.28, P values: 0.069, 0.126). Conclusions:Based on subjective scores and semi-quantitative indicators, 68Ga-PSMA PET/CT is superior to select β values of 600 and 700 for image reconstruction based on BSREMA. The SUV peak of small lesions is stable after PVC and the clinical value should be explored in further.
ABSTRACT
ABSTRACT Objective To evaluate the predictive value of positron emission computed tomography or magnetic resonance (PET-CT and PET-MRI) using gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA) in lymph node involvement in prostate cancer. Methods A retrospective study comprising 91 patients diagnosed with prostate cancer between 2016 to 2020, who underwent 68Ga-PSMA PET-CT or PET-MRI for staging before prostatectomy. The patients were divided into Group 1, with 65 patients with satisfactory pathological lymph node analysis, and Group 2, with 91 patients representing the sum of patients with pathological lymph node analysis and those with postoperative prostate-specific antigen within 60 days after surgery. Receiver Operating Characteristic curves were used to assess accuracy of predictive capacity of imaging exams for lymph node involvement. Results Regarding local clinical staging, the groups showed similar results, and 50% were classified as staging T2a. The accuracy of 68Ga-PSMA PET-CT for prostate cancer lymph node staging was 86.5% (95%CI 0.74-0.94; p=0.06), with a sensitivity of 58.3% and specificity of 95%. The accuracy of 68Ga-PSMA PET-MRI was 84.6% (95%CI 0.69-0.94; p=0.09), with a sensitivity of 40% and specificity of 100%. Considering both 68Ga-PSMA PET-CT and PET-MRI, the accuracy was 85.7% (95%CI 0.76-0.92; p=0.015), with sensitivity of 50% and specificity of 97%. Conclusion The imaging tests 68Ga-PSMA PET-CT and PET-MRI were highly accurate to detect preoperative lymph node involvement, and could be useful tools to indicate the need for extended lymph node dissection during radical prostatectomy.
ABSTRACT
@#Neuroendocrine tumours (NETs) are a category of neoplasm that is characterised by its phenotypic and heterogeneity. The occurrence of this type of neoplasm in the nasal cavity and paranasal sinuses is extremely rare accounting for only 0.2-0.8% of all cancers. NET tends to expresses somatostatin receptors (SSTR) and owning to this unique characteristic, molecular imaging has been able to detect these tumours using radiolabelled somatostatin analogue agent. Gallium-68 (Ga-68) DOTATATE PET/CT is an example of SSTR imaging and has been shown to be of importance in the assessment and staging of NET. We present a case of a rare sphenoid sinus NET in a 45-year-old gentleman whom initially presented with persistent left eye pain which led to visual loss. We described the utilization of Ga-68 DOTATATE PET/CT in the diagnosis and staging of this patient which in turn dictated treatment approach.