Comparison of 68GA-FAPI-04 PET/CT and 18F-FDG PET/CT in detection of metastatic bone disease in various cancers

ObjectiveOur aim in this retrospective study was to compare the diagnostic accuracy of ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT in detecting bone metastases of various cancers and to evaluate the potential usefulness of ⁶⁸Ga-FAPI-04 PET/CT in detecting metastatic bone disease.Material and methodOur retrospective study included 44 patients diagnosed with bone metastases due to various cancers between January 2021 and February 2022. All patients underwent ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT imaging within 14 days. In the semi-quantitative analysis of the skeletal system, all regions with higher uptake than background activity were considered pathological. SUVmax and Metastasis-to-background ratio (TBR) values were calculated from metastatic sites.ResultsA total of 827 bone metastases were detected in our study. The diagnostic accuracies of FAPI PET/CT and ¹⁸F-FDG PET/CT were 91.8% and 81.5%, respectively (P < 0.001). When all bone metastases were compared, the SUVmax of ⁶⁸Ga-FAPI-04 PET/CT was statistically significantly higher than that of ¹⁸F-FDG PET/CT (median 6.15 vs. 5.2; P < 0.001). When FDG and FAPI SUVmax values were compared according to metastasis types, FAPI SUVmax and TBR values in osteolytic, medullary and mixed type bone metastases were found to be statistically significantly higher than FDG (P-values: < 0.001, < 0.001, < 0.001, respectively). There was no statistically significant difference between FDG and FAPI SUVmax values in osteoblastic bone metastases (P = 0.26).ConclusionIt has been shown that ⁶⁸Ga-FAPI-04 PET/CT is superior to ¹⁸F-FDG PET/CT in detecting metastatic bone disease and may have more clinical impact on disease management.     

早期动态18F-FDG PET/CT成像在实体肿瘤评估中的应用

~(18)F-FDG PET/CT常规代谢成像反应肿瘤的葡萄糖代谢及乏氧情况,而~(18)F-FDG PET/CT早期动态成像能反映PET/CT成像早期肿瘤的灌注情况。由于肿瘤的异质性,在早期动态~(18)F-FDG PET/CT成像,即~(18)F-FDG PET/CT灌注成像中,存在独立于常规60 min~(18)F-FDG PET/CT代谢成像的SUVmax(最大标准摄取值)高摄取区。因此,在临床工作中应用~(18)F-FDG PET/CT早期动态成像,能够进一步对实体肿瘤的活性区域进行评估,能够更好评价患者预后、完善治疗方案。当前~(18)F-FDG早期动态成像已经应用在肝癌、肾癌以及膀胱癌等实体肿瘤诊断中。早期动态~(18)F-FDG PET/CT成像结合常规标准~(18)F-FDG PET/CT代谢成像,对实体肿块进行一站式成像方法,能够更好的对肿瘤进行评估。     

Performances de la TEP au 18F-FDG dans la caractérisation initiale de la lésion primitive du cancer du sein

Objective¹⁸F-FDG PET/CT is for the moment not recommended for stage T of the TNM classification of breast cancer. The aim of our study was to evaluate the performance of ¹⁸F-FDG PET/CT in the initial staging of breast tumors. Tumor size, skin involvement and inflammation as well as the relationship between primary tumor maximum standardized uptake value (SUVmax) and histopathological grade (SBR), molecular tumor subtypes (luminal A and B, Her2 enriched, triple negative), estrogen receptors (ER), progesterone receptors (PR) and focality were evaluated.MethodsHistological reports of patients operated for breast cancer, without neoadjuvant chemotherapy, were compared to preoperative ¹⁸F-FDG PET/CT.ResultsSeventy-four patients who underwent surgery in 2016 were included. ¹⁸F-FDG PET/CT was able to visualize primary tumors in 91% and to correctly classify the T stage of the TNM classification in 81% of the cases, to detect multifocality in 73% and cutaneous and inflammatory breast cancers in 100%. The uptake intensity of ¹⁸F-FDG (SUVmax) was significantly correlated with histo-prognostic factors such as SBR grade (P = 0.02), lack of expression of estrogen receptors (ER) (P = 0.01) and progesterone (PR) (P = 0.02), positive HER2 status (P = 0.01) or triple negative subtype tumors (P = 0.02).Conclusion¹⁸F-FDG PET/CT provides relevant elements for local assessment, in particular, tumor focality and inflammatory character in addition to ensuring the regional and extension assessment.     

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis

Purpose

To explore the value of a new simple lyophilized kit for labeling PRGD₂ peptide (¹⁸F-ALF-NOTA-PRGD₂, denoted as ¹⁸F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using ¹⁸F-fluorodeoxyglucose (FDG) PET.

Methods

All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers ¹⁸F-alfatide and ¹⁸F-FDG within two days. ¹⁸F-alfatide metabolic tumor volume (V_RGD) and ¹⁸F-FDG metabolic tumor volume (V_FDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (V_Path) was measured in vitro after the xenografts were removed.

Results

A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent ¹⁸F-alfatide PET, and 35 of them underwent ¹⁸F-FDG PET and all underwent pathological examination. The mean ± standard deviation of V_Path, V_RGD, and V_FDG were 0.59±0.32 cm³ (range,0.13~1.64 cm³), 0.61±0.37 cm³ (range,0.15~1.86 cm³), and 1.24±0.53 cm³ (range,0.17~2.20 cm³), respectively. V_Path vs. V_RGD, V_Path vs. V_FDG, and V_RGD vs. V_FDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between V_Path and V_RGD. V_FDG was much larger than V_RGD and V_Path. V_RGD seemed more approximate to the pathologic gross tumor volume. Furthermore, V_Path was more strongly correlated with V_RGD (R = 0.964,P<0.001) than with V_FDG (R = 0.584,P<0.001).

Conclusions

¹⁸F-alfatide PET provided a better estimation of gross tumor volume than ¹⁸F-FDG PET in LLC tumor-bearing C57BL/6 mice.     

Impact de la TEP/TDM au 18F-FDG dans la prise en charge des patients atteints de cancer thyroïdien différencié

Aim¹⁸F-FDG PET/CT by combining both metabolic and anatomical informations has proven to be an effective modality for detecting many types of cancer. Some differentiated forms of cancer like differentiated thyroid carcinoma (DTC) are less FDG avid and thus less easily detectable. Nevertheless ¹⁸F-FDG PET/CT has been proved useful in DTC especially in case of suspected recurrent disease with negative whole-body radioiodine scintigraphy (¹³¹I WBS) and elevated thyroglobulin (Tg) or thyroglobulin autoantibodies (AbTg) levels. Impact on clinical management after ¹⁸F-FDG PET/CT examinations has been analyzed in patients with suspected recurrent DTC in this retrospective study.MethodologyFifty-five ¹⁸F-FDG PET/CT were performed in 45 patients with suspected recurrent or residual disease either because of elevated Tg/AbTg levels (n = 45) or uncertain conventional imaging (n = 10) including ¹³¹I WBS, cervical echography and CT scan if necessary. ¹⁸F-FDG PET/CT results were compared with histopatology and/or clinical follow-up with evaluation of impact on clinical management.ResultsTwenty-nine exams were positive (53 %). There were 20 true-positive (TP) (14 locoregional relapses and six with distant metastases) and nine false-positive (FP) (all cervical). SUV_max median values of hypermetabolic foci were significantly higher in TP (5.1) than in FP (2.8). Overall, 20 (36 %) ¹⁸F-FDG PET/CT directly affected clinical management resulting in 13 (65 %) new surgical operations. Sensitivity, specificity, predictive positive value, predictive negative value and accuracy of ¹⁸F-FDG PET/CT were estimated for the whole group (respectively 83 %, 71 %, 69 %, 85 % and 76 %) and for two subgroups depending on Tg level (less or more than 1.2 ng/mL).Discussion and conclusion¹⁸F-FDG PET/CT is a powerful and useful tool in patients with suspected DTC recurrence or residual disease and should be systematically performed when basal Tg level is above 1.2 ng/mL. Thanks to given anatomical informations it can guide surgical re-operation.     

18F-FDG Micro PET/CT imaging to evaluate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity

ObjectiveRadioresistance of tumor cells is a major factor associated with failure of radiotherapy (RT). This study aimed to investigate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity.Materials and methodsShort hairpin RNA (shRNA) was used to knockdown BRCA1 gene in MDA-MB231 cells. Cell viability and proliferative capacity were assessed by CCK-8 and colony formation assays, respectively. We established xenograft models in nude mice to evaluate tumor volume and tumor weight. The mice were imaged by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) before and after RT to evaluate changes in maximum standardized uptake value (SUV_max) and tumor SUV_max/muscle SUV_max (TMR). Changes in HIF-1α, Glut-1 and Ki-67 were analyzed and the correlation between ¹⁸F-FDG uptake and tumor biology was analyzed.ResultsCompared with the control cells, RT significantly reduced cell viability and colony formation capacity in cells with the BRCA1 gene knockdown. In vivo assays showed that there was obvious delay in the tumor growth in the shBRCA1+RT group compared with the control group. ¹⁸F-FDG Micro PET/CT indicated a reduction in glucose metabolism in the shBRCA1+RT group, with statistically significant differences in both the SUV_max and TMR. The data showed the expression of HIF-1α, Glut-1 and Ki-67 was downregulated in the shBRCA1+RT group, and both SUVmax and TMR had significant correlation with tumor biology.ConclusionThese results demonstrated that BRCA1 knockdown improves the sensitivity of MDA-MB231 breast cancer cells to RT. In addition, ¹⁸F-FDG PET/CT imaging allows non-invasive analysis of tumor biology and assessment of radiosensitivity.     

Combined Injection of 18F-Fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET Achieves More Complete Identification of Viable Lung Cancer Cells in Mice and Patients than Individual Radiopharmaceutical: A Proof-of-Concept Study

PURPOSE: The objective is to validate the combination of 3′-deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) as a “novel” positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. METHODS: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of ¹⁸F-FDG, ¹⁸F-FLT, and the cocktail of ¹⁸F-FDG and ¹⁸F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, ¹⁸F-FDG PET and ¹⁸F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, ¹⁸F-FDG and ¹⁸F-FLT cocktail PET scan was also performed in the mouse. RESULTS: When injected individually, ¹⁸F-FDG highly accumulated in hypoxic zones and high ¹⁸F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlated with hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of ¹⁸F-FDG and ¹⁸F-FLT was generally mismatched in both rodents and patients. Combination of ¹⁸F-FLT and ¹⁸F-FDG appeared to map more cancer tissue than single-tracer PET. CONCLUSIONS: Combination of ¹⁸F-FDG and ¹⁸F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.     

Radiobiological risks in terms of effective dose and organ dose from 18F-FDG whole-body PET/CT procedures

IntroductionIntegrated Positron Emission Tomography (PET) with Computerized tomography (CT) (PET/CT) are widely used to diagnose, stage and track human diseases during whole body scanning. Multi-modality imaging is an interesting area of research that aims at acquiring united morphological-functional image information for accurate diagnosing and staging of the disease. However, PET/CT procedure accompanied with high radiation dose from CT and administered radioactivity. The aim of the present study was to estimate the patients’ dose from ¹⁸F-fluorodeoxyglucose imaging (18F-FDG) hybrid PET/CT whole body scan.Materials and methodsRADAR (Radiation Dose Assessment Resource) software was used to estimate the effective dose for 156 patients (110 (70.5%)) males and 46 (39.5%) female) examined using Discovery PET/CT 710, GE Medical Systems installed at Kuwait Cancer Control Center (KCCC).ResultsThe effective dose results presented in this PET/CT study ranged from (1.56–9.94 mSv). The effective dose was calculated to be 3.88 mSv in females and 3.71 mSv in males. The overall breast (female), lung, liver, kidney and thyroid were 7.4, 7.2, 5.2, 4, 3 and 2.9, respectively.For females, the body mass index (BMI) was 28.49 kg/m² and for males it was 26.50 kg/m² which showed overweight values for both genders. Conclusions: The findings indicate that the effective dose of 18F-FDG in both male and female patients was not substantially different. The study suggested that the risk–benefit proportions of any ¹⁸F-FDG whole body PET/CT scan should be clarified and carefully weighed. Patient’s doses are lower compared with previous studies.     

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using ¹⁸F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as ¹⁸F-Fluorocholine (¹⁸F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer ¹⁸F-FCH/¹⁸F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to ¹⁸F-FCH and ¹⁸F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The ¹⁸F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in ¹⁸F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by ¹⁸F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of ¹⁸F-FCH/ ¹⁸F-FDG-PET imaging in this study, while the false-positive caused by ¹⁸F-FCH can be eliminated. Dual tracer ¹⁸F-FCH/¹⁸F-FDG PET imaging has the potential to improve the visualization of low grade glioma. ¹⁸F-FCH delineates tumor areas and the tumor can be identified by subtracting the ¹⁸F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.     

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

This study revisited ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake and its relationship to hypoxia in various tumor models. METHODS: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non–small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO₂) of ascites fluid was measured. ¹⁸F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections. RESULTS: Ascites pO₂ was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high ¹⁸F-FDG uptake. In contrast, ¹⁸F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver. CONCLUSIONS: Glucose demand (¹⁸F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of ¹⁸F-FDG PET in oncology application.     

Ostéomyélite de l’apophyse odontoïde : intérêt de la TEP/TDM au 18F-FDG dans le bilan d’extension infectieux à distance

Odontoid process is an atypical and very rare localization of osteomyelitis. We reported the case of a 72-year-old hemodialysed man with methicillin-sensitive Staphylococcus aureus osteomyelitis of the odontoid process. Osteomyelitis was diagnosed at MRI and ¹⁸F-FDG PET/CT. While clinical examination and conventional radiographs were non contributive, ¹⁸F-FDG PET/CT also allowed the diagnosis of right foot osteomylitis and multiple vertebral septic localizations. ¹⁸F-FDG PET/CT done at month 3 demonstrated a regression of the odontoid and foot hypermetabolic activity. This case illustrates the atypical presentation of this septic localization and the usefulness of ¹⁸F-FDG PET/CT to perform whole body screening and detect septic metastasis.     

Intérêt pronostique et prédictif de la TEP-TDM au 18F-FDG au bilan initial des mélanomes de stade IIIB-C-D et IV avant traitement par anti-PD-1

PurposeThe advent of immunotherapy by checkpoint inhibitor has profoundly changed the prognosis of patients with metastatic melanoma. The objective of our study was to evaluate the prognostic and predictive performance of 18F-FDG PET/CT of the initial extension assessment of stage IIIB-C-D and IV melanomas.MethodsWe retrospectively included 57 patients who had 18F-FDG PET/CT prior to the introduction of anti-PD-1 immunotherapy. The parameters extracted were SUVmax, SUV peak, MTV and TLG of the lesion with highest uptake (MTV LM, TLG LM), as well as MTV total and TLG total, obtained by adaptive segmentation. The18F-FDG PET/CT were dichotomized using the optimal threshold measured according to the area under the curve in the ROC (Receiver Operation Characteristic) curves. These parameters were evaluated using a Cox model. Overall survival and progression-free survival analyses were performed using the Kaplan Meier model.ResultsThe median follow-up was 25.4 months, 38 patients had progressed or recurred, and 20 patients had died. TLG LM > 132.59 (P = 0.0011), MTV total > 12 cm³ (P = 0.0139), and TLG > 94.17 (P = 0.0084) were significantly associated with a shorter progression-free survival. TLG LM > 145.92 (P = 0.0062), MTV total > 10.16 cm³ (P = 0.0051), and a metastatic spread > 2 organs (P = 0.0001) were associated with a shorter overall survival.ConclusionWe confirm the potential prognostic interest of PET-TDM at 18FDG before immunotherapy of stage IIIB-C-D and IV melanomas on progression-free survival and overall survival. The combination of these metabolic markers reflecting tumor burden with clinical and biological prognostic factors could allow early identification of patients at high risk of anti-PD-1 failure.     

18F-FDG PET Imaging of Murine Atherosclerosis: Association with Gene Expression of Key Molecular Markers

Aim

To study whether ¹⁸F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between ¹⁸F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE^−/− mice.

Methods

Nine groups of apoE^−/− mice were given normal chow or high-fat diet. At different time-points, ¹⁸F-FDG PET/contrast-enhanced CT scans were performed on dedicated animal scanners. After scans, animals were euthanized, aortas removed, gamma counted, RNA extracted from the tissue, and gene expression of chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, cluster of differentiation molecule (CD)-68, osteopontin (OPN), lectin-like oxidized LDL-receptor (LOX)-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR.

Results

The uptake of ¹⁸F-FDG increased over time in the groups of mice receiving high-fat diet measured by PET and ex vivo gamma counting. The gene expression of all examined markers of atherosclerosis correlated significantly with ¹⁸F-FDG uptake. The strongest correlation was seen with TF and CD68 (p<0.001). A multivariate analysis showed CD68, OPN, TF, and VCAM-1 to be the most important contributors to the uptake of ¹⁸F-FDG. Together they could explain 60% of the ¹⁸F-FDG uptake.

Conclusion

We have demonstrated that ¹⁸F-FDG can be used to follow the progression of atherosclerosis in apoE^−/− mice. The gene expression of ten molecular markers representing different molecular processes important for atherosclerosis was shown to correlate with the uptake of ¹⁸F-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake.     

Does 18F-FDG Positron Emission Tomography-Computed Tomography Have a Role in Initial Staging of Hepatocellular Carcinoma?

Background and Aim

The utility of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of ¹⁸F-FDG PET/CT in initial staging of HCC.

Methods

A total of 457 consecutive patients initially diagnosed with HCC at Seoul National University Hospital between 2006 and 2012 were evaluated retrospectively to assess the impact of ¹⁸F-FDG PET/CT on staging and compliancy with Milan criteria, relative to dynamic CT of liver and chest x-ray.

Results

Seven among the 457 patients studied showed a shift in Barcelona Clinic Liver Cancer [BCLC] stage (A→C: 6 patients; B→C: 1 patient) and 5 patients who had originally met Milan criteria no longer qualified. ¹⁸F-FDG PET/CT had value in initial staging of early (stage A) or intermediate (stage B) HCC, as determined by dynamic CT of liver and BCLC or AJCC classifications, whereas BCLC stage 0 and stage C tumors were unchanged (P<0.001). ¹⁸F-FDG PET/CT disclosed additional metastases in patients with American Joint Committee on Cancer [AJCC] T2 (2.7%), T3a (5.3%), and T3b (4.8%) classifications.

Conclusions

In initial staging of HCC, ¹⁸F-FDG PET/CT provided additional information, impacting the patients with BCLC (stages A and B) and AJCC (T2 and T3) classifications. Its use might be thus appropriate for these patient subsets, especially if hepatic resection or liver transplantation is planned.     

Quantification and monitoring of PET/CT data in multicentre trials: The Swiss SAKK 56/07 trial experience

AimTo outline the importance of continuous monitoring of quantitative positron emission tomography (PET) data in multicentre trials to minimize quantitative bias in longitudinal intra-patient PET studies in light of the multicentre SAKK 56/07 experience in quantification and monitoring ¹⁸F-FDG PET/CT data.Patients and methodsWe collected 64 uniform phantom ¹⁸F-FDG PET acquisitions periodically at the enrolling centres (12 European institutions). A core-laboratory analysed them for standard uptake value (SUV) accuracy (desired 1.00 ± 10%) and acceptable image noise was defined by a coefficient of variation (COV) less than 15%. In total, 151 patients ¹⁸F-FDG PET acquisitions (baseline and follow-up) were also collected and analysed to verify longitudinal coherence of main acquisition/reconstruction parameters (DICOM tags verification) and patient preparation, in particular the uptake time (desired uptake time [UT] = 60 ± 10 min).ResultsUniform phantom PET acquisition satisfied the inclusion criteria in 58/64 (89%) examinations. All PET scanner exhibited comparable SUV quantification, but we found large dispersion in terms of noise, with COV ranging 3–15%. Only 1 phantom PET acquisition was out of range with COV = 21.5%. Patient data exhibited important variation in uptake time with UT = 65 ± 10 min (mean ± SD), with only 111/151 (74%) patients’ examinations satisfying inclusion criteria while 26% were out of range.ConclusionsRegular monitoring of PET data in multicentre trials is capital to ensure longitudinal intra-patient PET data consistence and minimize quantitative bias while it helps to spread the culture of quality in participating centre. Recent EARL (EANM Research Ltd) standardization and unification of procedures is a welcome step in this direction.     

Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma

BackgroundWe investigated the relationship between genetic alterations and ¹⁸F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC).MethodsUsing mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on ¹⁸F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDG_SS). The FDG_SS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways.FindingsThe FDG_SS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDG_SS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDG_SS positively correlated with total mutation rate (p = 0.016), aneuploidy (p < 0.001), and somatic copy number alteration scores (p < 0.001). CDKN2A in the cell cycle pathway (q = 0.014) and the TP53 gene in the TP53 pathway (q = 0.005) showed significant differences between high and low FDG_SS patients.ConclusionFDG_SS based on the gene coexpression network was associated with the mutational landscape of HNSC. ¹⁸F-FDG PET/CT is therefore a valuable tool for the in vivo imaging of these cancers, being able to visualize the glucose metabolism of the tumor and allow inferences to be made on the underlying genetic alterations in the tumor.     

Synthesis and evaluation of Al18F-NODA complex conjugated 2-(4-aminophenyl)benzothiazole as a potential tumor imaging agent

The objective of the study was to prepare and evaluate a ¹⁸F-radiolabled tracer (Al¹⁸F-5), derivated from the antitumor agent 2-(4-aminophenyl)benzothiazole, as a PET probe for tumor imaging. Al¹⁸F-5 was successfully prepared with approx. 40% radiochemical yield in aqueous phase. In in vitro cell uptake experiments and competition assay, Al¹⁸F-5 displayed good tumor-binding ability and specificity in HeLa cells (24.7 ± 0.9% ID/10⁶ cells, IC₅₀ = 63.8 ± 13.6 nM) and MCF-7 cells (6.8 ± 0.3% ID/10⁶ cells, IC₅₀ = 331.1 ± 33.7 nM). The nonradioactive compound, Al¹⁹F-5, visibly marked HeLa cells and MCF-7 cells but did not stain HEB cells in florescent staining, which further indicated the tumor-binding ability of Al¹⁸F-5. In in vivo PET imaging, HeLa and MCF-7 tumors were clearly delineated by specific accumulation of Al¹⁸F-5 in model mice. In biodistribution study, Al¹⁸F-5 exhibited good tumor uptake (4.66 ± 0.13% ID/g and 3.69 ± 0.56% ID/g, respectively), moderate tumor-to-muscle ratio (3.38 and 2.48, respectively) at 1 h post injection, which were in a good consistency with the results of PET imaging. In conclusion, Al¹⁸F-5 might be developed as a candidate PET probe for tumor imaging, though additional optimizations are still needed to improve pharmacokinetics in vivo.     

Synthesis and preclinical characterization of 1-(6′-deoxy-6′-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6′-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia

Positron emission tomography (PET) using fluorine-18 (¹⁸F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6′-deoxy-6′-[¹⁸F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[¹⁸F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [¹⁸F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12 ± 8% (n = 10, based on [¹⁸F]fluoride starting activity) in a total synthesis time of 60 min with a specific activity at end of synthesis of 218 ± 58 GBq/μmol (n = 10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[¹⁸F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[¹⁸F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13 ± 0.22 (n = 4) at 2 h after administration of β-[¹⁸F]1. In ex vivo autoradiography experiments β-[¹⁸F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[¹⁸F]1 shows potential as PET hypoxia radiotracer which merits further investigation.     

Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice

Background

3′-deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use ¹⁸F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET.

Methodology/Principal Findings

In vivo uptake of ¹⁸F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline ¹⁸F-FLT scans were made before either Top216 (n = 7–10) or vehicle (n = 5–7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2′-deoxy-2′-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). ¹⁸F-FLT uptake decreased significantly at 2 hours (−52%; P<0.001), 6 hours (−49%; P = 0.002) and Day 1 (−47%; P<0.001) after Top216 treatment. At Day 5 ¹⁸F-FLT uptake was comparable to uptake in the control group. Uptake of ¹⁸F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of ¹⁸F-FDG was significantly decreased at 6 hours (−21%; P = 0.003), Day 1 (−29%; P<0.001) and Day 5 (−19%; P = 0.05) compared to baseline.

Conclusions/Significance

One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by ¹⁸F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that ¹⁸F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.     

Radiosynthesis and preclinical evaluation of [18F]FEM as a potential novel PET probe for tumor imaging

In the 21st century, the incidence and mortality of cancer, one of the most challenging diseases in the world, have rapidly increased. The purpose of this study was to develop 2-(2-[¹⁸F]fluoroethoxy)ethyl 4-methylbenzenesulfonate ([¹⁸F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, [¹⁸F]FEM was synthesized with a good radiochemical yield (45.4 ± 5.8%), high specific radioactivity (over 25 GBq/μmol), and commendable radiochemical purity (over 99%). The octanol/water partition coefficient of [¹⁸F]FEM was 1.44 ± 0.04. The probe demonstrated good stability in vitro (phosphate-buffered saline (PBS) and mouse serum (MS)), and binding specificity to five different tumor cell lines (A549, PC-3, HCC827, U87, and MDA-MB-231). PET imaging of tumor-bearing mice showed that [¹⁸F]FEM specifically accumulated at the tumor site of the five different tumor cell lines. The average tumor-to-muscle (T/M) ratio was over 2, and the maximum T/M values reached about 3.5. The biodistribution and dynamic PET imaging showed that most probes were metabolized by the liver, whereas a small part was metabolized by the kidney. Moreover, dynamic brain images and quantitative data showed [¹⁸F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out, thereby suggesting it may be a promising candidate probe for the imaging of brain tumors. The presented results demonstrated that [¹⁸F]FEM is a promising probe for tumor PET imaging.