Tumor Uptake Values Research Articles

Design, Synthesis, and Biological Evaluation of 4-Arylamino Pyrimidine Derivatives as FAK Inhibitors and Tumor Radiotracers

Focal adhesion kinase (FAK) is considered a promising target for the diagnosis and treatment of cancer. In this work, a series of N,N'-(4-((5-bromo-2-(phenylamino)pyrimidin-4-yl)amino)-1,3-phenylene)diacetamide derivatives were synthesized and evaluated as FAK inhibitors and radiotracers. The studied compounds, possessing the same phenylene-diacetamide chain, exhibited high to moderate enzyme inhibition values (IC50) ranging from 3.7 to 108.0 nM. Compound 13a, which exhibits high FAK enzyme inhibition with an IC50 value of 3.7, could effectively suppress the tumor growth. Furthermore, three compounds were radiolabeled with F-18. Among them, a higher tumor uptake value was observed for [18F]17 (3.73 ± 0.10% ID/g) and [18F]13a (3.66 ± 0.02% ID/g). Compound [18F]18 displayed the highest tumor/blood (35.75) value at 120 min postinjection. In addition, the results from docking studies revealed the binding mechanism of the studied compounds. The findings of this study may provide useful guidance to improve the development of radiotracers and enzyme inhibitors.

Effects of cigarette smoking on metabolic activity of lung cancer on baseline 18F-FDG PET/CT.

BackgroundNever-smokers with lung cancer usually have a higher survival rate than that of smokers. The high metabolic activity of lung cancer on 18F-2-Fluoro-2-deoxyglucose (18F-FDG) PET/CT generally indicates a poor outcome. However, there is a lack of reports on the association between cigarette smoking and 18F-FDG metabolic activity in patients with lung cancer. In this study, we aimed to investigate the effects of cigarette smoking on metabolic activity of lung cancer on 18F-FDG PET/CT.Materials and MethodsA total of 338 patients (230 males, 108 females; mean age: 66.3, range 34–86) with pathologically diagnosed lung cancer were enrolled from September 2019 to April 2021. All patients underwent baseline 18F-FDG PET/CT and the maximum standard uptake value (SUVmax) of the primary tumor (pSUVmax), lymph node (nSUVmax) and distant metastasis (mSUVmax) were measured. The associations between cigarette smoking status, clinical stage, pathological subtypes and metabolic parameters on 18F-FDG PET/CT were analyzed.ResultsOf the 338 patients, cigarette smoking was identified in 153 patients (45.3%) and the remaining 185 (54.7%) were never-smokers. Smoking was found more frequently in males, squamous cell carcinoma (SCC) and stage III–IV diseases. The pSUVmax in smokers was significantly higher than that in never-smokers (t = 3.386, P < 0.001), but the nSUVmax and mSUVmax revealed no statistically significant differences (t = 0.399, P = 0.690 and t = 0.057, P = 0.955; respectively). With the increase of cumulative smoking dose, pSUVmax increased significantly (r = 0.217, P < 0.001). In addition, the pSUVmax in patients with stage III–IV was significantly higher than that in stage I–II (t = 8.509, P < 0.001). Smokers showed a higher pSUVmax than never-smokers for patients with stage I–II (t = 3.106, P = 0.002), but not in stage III–IV (t = 0.493, P = 0.622). The pSUVmax was significantly different among patients with different pathological subtypes of lung cancer (F = 11.45, P < 0.001), while only the adenocarcinoma (ADC) and SCC groups showed a difference in pSUVmax (t = 6.667, P < 0.001). Smokers with ADC showed a higher pSUVmax when compared to never-smokers, but not in SCC. There were no significant differences of pSUVmax between smokers and never-smokers at stage I–II ADC or SCC and stage III–IV ADC or SCC.ConclusionsThis study demonstrated a close association between cigarette smoking and the metabolic activity of lung cancer and suggests that smoking may be a potential risk factor of higher pSUVmax in early lung cancer on 18F-FDG PET/CT.

Design, synthesis, and preclinical evaluation of a novel bifunctional macrocyclic chelator for theranostics of cancers.

This study was to design and synthesize a novel bifunctional chelator, named Dar, primarily validated by conjugating to tumor targeting motifs, labeled with radiometals, and performed preclinical evaluation of tumor imaging and cancer therapy in murine tumor models. The designed Dar was synthesized and characterized by X-ray crystallography, 1H/13C NMR, and mass spectrometry. Dar-PSMA-617 was conjugated and radiolabeled with 68Ga, 177Lu, and 89Zr. The in vivo behavior of 68Ga/89Zr-labeled Dar-PSMA-617 were evaluated using micro-PET imaging and biodistribution from image quantitation and tissue radioactivity counting, with 68Ga/89Zr-labeled NOTA/DOTA/DFO-PSMA-617 analogs as controls, respectively. The [177Lu]-Dar-PSMA-617, with [177Lu]-DOTA-PSMA-617 as control, was evaluated in competitive cell uptake, tumor cell internalization, and efflux studies. The treatment efficacy of [177Lu]Lu-Dar-PSMA-617, with [177Lu]Lu-DOTA-PSMA-617 as control, was evaluated in PSMA-positive LNCaP tumor-bearing mice. In addition, the ability of Dar for radiolabeling nanobody was tested by conjugating Dar to KN035 nanobody. The resultant [89Zr]Zr-Dar-KN035 nanobody, with [89Zr]Zr-DFO-KN035 as control, was evaluated by micro-PET imaging and biodistribution in a mouse model bearing MC38&MC38-hPD-L1 colon cancer. 68Ga, 89Zr, and 177Lu-radiolabeled Dar-PSMA-617 complexes were able to be produced under mild condition with high radiochemical yield and purity successfully. [177Lu]Lu-Dar-PSMA-617 had higher cellular uptake yet similar internalization and efflux properties in LNCaP cells, as compared to [177Lu]Lu-DOTA-PSMA-617. Micro-PET images demonstrated significantly higher tumor uptake of [68Ga]Ga-Dar-PSMA-617, than that of the analog [68Ga]Ga-DOTA-PSMA-617. The tumor uptake values of [68Ga]Ga-Dar-PSMA-617 at multiple time points are comparable to that of [68Ga]Ga-NOTA-PSMA-617, although a higher and persistently prolonged kidney retention was resulted in during the study period. The Dar chelator can also successfully mediate the radiolabeling with 89Zr, while the resultant [89Zr]Zr-Dar-PSMA-617 demonstrated a similar biodistribution with [89Zr]Zr-DFO-PSMA-617 measured at 96h p.i. The treatment with [177Lu]Lu-Dar-PSMA-617 significantly inhibited the tumor growth, showing much better efficacy than that of [177Lu]Lu-DOTA-PSMA-617 at the same injected radioactivity and mass dose. Dar was covalently linked to KN035 nanobody and enabled radiolabeling with 89Zr in high yield and radiochemical purity at room temperature. The resultant [89Zr]Zr-Dar-KN035, with [89Zr]Zr-DFO-KN035 as control, demonstrated superior tumor uptake and detection capability in PET imaging studies. The Dar, as a novel bifunctional chelator for medicating the labeling of radiometals onto tumor targeting carriers, was successfully synthesized and chemically characterized. Test radiolabeling, on PSMA-617 and a nanobody as tool targeting molecule carriers, demonstrated the Dar has potential as a universal bifunctional chelator for radiolabeling various radiometals (at least 68Ga, 177Lu, and 89Zr tested) commonly used for clinical imaging and therapy. Using a novel Dar chelator results in altered in vivo behavior of the carriers even though labeled with the same nuclide. This capability makes Dar an alternative to the existing choices for radiolabeling new carrier molecules with various radiometals, especially the radiometals with large radius.

Can the Ratio SUVmax of the Lesion/SUVmax of Mediastinal Tissues Guide the Choice of Surgical Access for the Resection of Thymic Epithelial Tumors?

BackgroundThere are studies showing the utility of the 18-fluorodeoxyglucose positron emission tomography (18FDG PET) scan in the management of patients with thymic epithelial tumors. It seems to be a correlation between the standard uptake value (SUVmax) of thymic epithelial tumors and the histological type and the stage. This study aims to use the ratio of the SUVmax of the lesion to the SUVmax of the adjacent mediastinal tissues in order to guide the choice of the surgical access.MethodsAll patients who presented an anterior mediastinal lesion with a high suspicion of being of thymic origin were included in a prospective database. A ratio inferior to 1 could predict a benign nature and less aggressive behavior, and a minimally invasive approach was performed. A ratio superior to 1 suggested a malignant and aggressive behavior, and a median sternotomy (or a thoracotomy) was performed.ResultsThere were 15 male (mean age 44.6 ± 16.26 years, range 25–73) and 15 female patients (mean age 50.1 ± 16.94 years, range 25–76). When the ratio is inferior to 1, it predicts benign disease in 80% of cases. When it is superior to 1, it predicts in half of cases advanced histological types (high risk thymomas and thymic carcinomas). On the contrary, it can quite accurately predict advanced Masaoka–Koga stages.ConclusionsThe protocol of this study is in accordance with the current literature showing the utility of 18FDG PET scan in the treatment of thymic epithelial tumors. This study goes one step further since the choice of surgical access is based on the SUVmax values. The ratio SUVmax of the lesion/SUVmax of the mediastinal tissues could be a new marker, more pertinent than absolute SUVmax values.

Synthesis and biological evaluation of a &amp;lt;sup&amp;gt;99m&amp;lt;/sup&amp;gt;Tc-labeled glucose derivative for tumor imaging

<p indent="0mm">The development of novel tumor-imaging agents for single-photon-emission-computed tomography (SPECT) with good performance, simple preparation and low price is a hot topic in the field of radiopharmaceutical research. ^99mTc is the most widely used SPECT nuclide in clinic. In order to develop a novel ^99mTc-labeled tumor radiopharmaceuticals, in this study, a glucose derivative (CN6DG) containing isonitriles was synthesized and it was radiolabeled with ^99mTc to obtain the ^99mTc-CN6DG complex with high radiochemical purity (&gt;95%). The complex is hydrophilic (log<italic>D</italic>=−2.52±0.33) and has good stability <italic>in vitro </italic>and<italic> in vivo</italic>. <italic>In vitro</italic> cell-uptake assay showed that tumor cells uptake of the complex was related to glucose transporters. In S180 tumor-bearing mice <sc>2 h</sc> after injection, the tumor-uptake value was 0.75±0.12 %ID/g and the tumor/muscle, tumor/blood ratios were 4.41 and 18.75, respectively. In A549 tumor-bearing mice after <sc>2 h</sc> of post-injection, the tumor-uptake value was 2.62±0.23 %ID/g, which was higher than that of ^99mTc-CN5DG (1.48±0.23 %ID/g). Its tumor/blood (52.4 <italic>vs</italic>. 49.33) ratios and tumor/muscle ratios (6.89 <italic>vs</italic>. 24.67) were as good as that of ^99mTc-CN5DG. The SPECT/CT imaging results in S180 and A549 tumor-bearing mice showed that it had significant tumor uptakes, indicating that it is a promising tumor-imaging agent.

Comparison of ten predictive equations for estimating lean body mass with dual-energy X-ray absorptiometry in older patients.

White fat contributes to body weight (BW) but accumulates very little [18F]fluorodeoxyglucose ([18F]FDG) in the fasting state. As a result, higher standardised uptake values normalised to BW (SUV) are observed in non-fatty tissue in obese patients compared to those in non-obese patients. Therefore, SUV normalised to lean body mass (SUL) that makes tumour uptake values less dependent on patients' body habitus is considered more appropriate. This study aimed to assess ten mathematical equations to predict lean body mass (LBM) by comparison with dual-energy X-ray absorptiometry (DXA) as the reference method. DXA-based LBM was compared with ten equation-based estimates of LBM in terms of the slope, bias and 95% limits of agreement (LOA) of Bland-Altman plots, and Pearson correlation coefficients (r). Data from 747 men and 811 women aged 60-65 years were included. Gallagher's equation was optimal in males (slope = 0.13, bias = -2.4 kg, LOA = 12.8 kg and r = 0.900) while Janmahasatian's equation was optimal in females (slope = 0.14, bias = -0.9 kg, LOA = 10.7 kg and r = 0.876). Janmahasatian's equation performed slightly better than Gallagher's in the pooled male and female data (slope = 0.00, bias = -1.6 kg, LOA = 12.3 kg and r = 0.959). The Gallagher and Janmahasatian equations were optimal and almost indistinguishable in predicting LBM in subjects aged 60-65 years. Determination of the optimum equation for predicting lean body mass to improve the calculation of SUL for [18F]FDG PET quantification.

The relationship of PET/CT SUVmax with EGFR mutation status and ALK rearrangement in lung adenocarcinoma.

Epidermal growth factor receptor mutations (EGFRm) and rearrangement of the anaplastic lymphoma kinase gene (ALKr) can be targeted for precision therapy in lung adenocarcinoma (LADC). As molecular profiling is not available for all, patient stratification can be achieved using non-invasive and economic tools, such as positron emission tomography/computed tomography (PET/CT). We aimed to evaluate the relationships between fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT maximum standardized uptake value (SUVmax) of primary tumors (pSUVmax) and lymph nodes (nSUVmax) and the EGFRm and ALKr status in a large series of Turkish LADC patients. In this retrospective study, medical records of histopathologically confirmed LADC patients were reviewed for demographic and clinical data. The 18F-FDG PET/CT pSUVmax nSUVmax were calculated and analyzed for their relationships with EGFRm and ALKr using multiple regression analysis. The study population consisted of 732 LADC patients with a mean age of 63±10 years. The frequencies of EGFRm and ALKr were 10.4% and 3.6%, respectively. Female gender, being a former- or never-smoker for EGFRm and age for ALKr were determined as independent risk factors (P<0.05). No significant differences in pSUVmax and nSUVmax were present between the patients with either EGFRm or ALKr compared to the wild-type genotype patients (P>0.05). We conclude that 18F-FDG PET/CT semi-quantitative parameter SUVmax could not be validated for the prediction of the EGFRm or the ALKr in our large series of 732 Turkish patients with LADC.

Prognostic value of 18F-FDG PET/CT and MRI features in patients with high-risk and very-high-risk cutaneous squamous cell carcinoma.

This study aimed to evaluate the prognostic value of 18F-fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and MRI features in patients with high-risk and very-high-risk cutaneous squamous cell carcinoma (cSCC). This study included 54 consecutive patients with surgically resected primary high-risk and very-high-risk cSCC who underwent pre-operative FDG-PET/CT and/or MRI. Among them, 14 patients (26%) had recurrences. We retrospectively reviewed the FDG-PET/CT (n = 34) and MRI (n = 48) and investigated the clinical significance and prognostic value of imaging features in cSCC. On FDG-PET/CT, the maximum standardized uptake value (SUVmax) of the primary tumor (13.0 ± 6.4 vs. 6.9 ± 5.3, p < 0.05) was higher in cSCC with recurrence than in cSCC without recurrence. On MRI, the maximum diameter of the lesion (46.8 ± 24.1 mm vs 30.4 ± 17.0 mm, p < 0.05) and the frequency of muscle/tendon/bone invasion (42% vs 11%, p < 0.05) were significantly greater in cSCC with recurrence than in cSCC without recurrence. In the univariate analysis, prognostic factors for recurrence were SUVmax of the primary tumor (p < 0.01), the maximum diameter of the lesion (p < 0.05), and depth of invasion (p < 0.05). The areas under the receiver operating characteristic curves of the SUVmax (0.78) were superior to those of the maximum diameter (0.71) and depth of invasion (0.60). SUVmax, maximum diameter, and depth of invasion were useful parameters for prognostic factors predicting recurrence in patients with high-risk and very-high-risk cSCC. SUVmax represents a prognostic factor.

Preoperative Body Composition Combined with Tumor Metabolism Analysis by PET/CT Is Associated with Disease-Free Survival in Patients with NSCLC.

Objective To evaluate the relationship between preoperative primary tumor metabolism and body composition in patients with NSCLC and analyze their effects on DFS. Method A retrospective study was conducted on 154 patients with NSCLC. All patients were scanned by baseline 18F-FDG PET/CT. SUVmax (maximum standard uptake value) of primary tumor, liver SUVmean (mean standard uptake value), and spleen SUVmean were measured by AW workstation. The skeletal muscle area (SMA), skeletal muscle mass index (SMI), skeletal muscle radiation density (SMD), visceral fat area (VFA), visceral adipose tissue index (VATI), and skeletal muscle visceral fat ratio (SVR) were measured by ImageJ software. Kaplan–Meier survival analysis was used to evaluate the impact of the above parameters on DFS. Results Compared with the low SUVmax group of primary tumors, the mean values of SMA, VFA, and VATI in the high SUVmax group were significantly higher. In addition, there were obvious differences in histopathological type, pathological differentiation, AJCC stage, and T stage between the two groups. Univariate analysis of DFS showed that VFA, VATI, pathological differentiation, tumor SUVmax, AJCC stage, tumor T stage, and N stage all affected the DFS of patients except for the parameters reflecting skeletal muscle content. Multivariate regression analysis showed that only VFA and SUVmax were associated with DFS. Kaplan–Meier survival analysis showed that high SUVmax, low VFA, high T stage, and high N stage were related to the decrease of DFS. Conclusion：Preoperative 18F-FDG PET/CT could comprehensively evaluate the primary tumor SUVmax, skeletal muscle, and visceral fat in patients with NSCLC. The combination of primary tumor SUVmax and visceral fat area can well evaluate the prognosis of patients with NSCLC.

Prognostic Role of 18F-FDG Positron Emission Tomography in Patients with Resectable Hepatocellular Carcinoma

Introduction: 18F-fluorodeoxyglucose positron emission tomography(18F-FDG PET) could predict tumour biology and aggressive of hepatocellular carcinoma(HCC). We hypothesized that 18F-FDG PET predicted survival of patients with HCC who underwent hepatectomy. Method: This was a retrospective study at a university center in Hong Kong. Data was retrieved from a prospectively entered database. Maximum standard uptake value(SUVmax) of tumor/ normal liver uptake(T/L ratio) was recorded. The PET positivity for overall survival(OS) was determined using T/L ratio by c-statistics using receiver operating characteristic curve. Multivariate analyses with preoperative, pathological variables and PET positivity were performed to determine the prognostic significance of post-hepatectomy OS and recurrence. Results: From 2004 to 2019, 267 patients who had 18F-FDG PET before hepatectomy. The 5-year OS and disease free survival(DFS) were 64.8% and 40.5% respectively. The median follow-up was 45.3 months. Table 1 showed the baseline demographics, operative and pathological characteristics of all patients. The optimal cut-off of T/L ratio was 1.526 based on ROC(AUC 0.674, 95% CI 0.608-0.741, P<0.001). Using a T/L ratio cutoff at 1.526, it was found to be an independent predictor of OS [hazard ratio(HR) 1.762 (1.120-2.773), p=0.014] (Table2) and was associated with a better OS.(Figure1) PET positive HCC were more likely to recur (with 5-year DFS 45.8% vs. 33.1%, p=0.001) and had a shorter DFS (median survival 8.5 vs 50 months, p=0.001).(Figure 2) Conclusion: PET positivity using T/L ratio was an independent factor for OS in HCC patients who underwent hepatectomy. 18F-FDG PET could be explored as a potential radiological biomarkers for HCC aggressiveness.

What a difference a methylene makes: replacing Glu with Asp or Aad in the Lys-urea-Glu pharmacophore of PSMA-targeting radioligands to reduce kidney and salivary gland uptake.

The aim of this study was to investigate the effect of replacing Glu in the Lys-urea-Glu PSMA-targeting pharmacophore of [68Ga]Ga-HTK03041 with a close analog on the uptake of kidneys, salivary glands and PSMA-expressing tumor xenografts.Methods: HTK03161, HTK03149 and HTK03189A/B were obtained by replacing Glu in HTK03041 with Asp, Aad (L-2-aminoadipic acid) and Api (2-aminopimelic acid), respectively. PSMA binding affinities were measured by competition binding assays. PET imaging and biodistribution studies of 68Ga-labeled ligands were performed in LNCaP tumor-bearing mice. The best candidate HTK03149 was selected and radiolabeled with 177Lu, and SPECT imaging and biodistribution studies were performed in LNCaP tumor-bearing mice. Radiation dosimetry calculation was conducted using the OLINDA software. Radioligand therapy study was performed in LNCaP tumor-bearing mice treated with [177Lu]Lu-HTK03149 (9.3-148 MBq), [177Lu]Lu-PSMA-617 (37 MBq) or natLu-HTK03149 (500 pmol).Results: PSMA binding affinities (Ki) of Ga-HTK03161, Ga-HTK03149, Ga-HTK03189A and Lu-HTK03149 were 3.88±0.66, 6.99±0.80, 550±35.7 and 1.57±0.42 nM, respectively. PET imaging showed that all 68Ga-labeled HTK03161, HTK03149 and HTK03189A/B were excreted mainly via the renal pathway and had minimal uptake in all organs/tissues including kidneys and salivary glands. Tumor xenografts were clearly visualized in PET images of [68Ga]Ga-HTK03161 and [68Ga]Ga-HTK03149 but were barely visualized using [68Ga]Ga-HTK03189A/B. Tumor uptake values for [68Ga]Ga-HTK03161, [68Ga]Ga-HTK03149, [68Ga]Ga-HTK0189A and [68Ga]Ga-HTK03189B were 12.7±1.91, 19.1±6.37, 2.10±0.28 and 0.67±0.15 %IA/g, respectively at 1h post-injection, and their average kidney and salivary gland uptake values were 2.13-4.41 and 0.20-0.23 %IA/g, respectively. Longitudinal SPECT imaging studies showed that [177Lu]Lu-HTK03149 was excreted mainly through the renal pathway with high uptake in LNCaP tumors and minimal uptake in all normal organs/tissues. The tumor uptake of [177Lu]Lu-HTK03149 peaked at 4h post-injection (20.9±2.99 %IA/g) and the uptake was sustained over time. Compared to [177Lu]Lu-PSMA-617, [177Lu]Lu-HTK03149 had 145% increase in tumor absorbed dose but 70% less in kidney absorbed dose, leading to an 7.1-fold increase in tumor-to-kidney absorbed dose ratio. Radioligand therapy studies showed that only half of the [177Lu]Lu-PSMA-617 injected dosage was needed for [177Lu]Lu-HTK03149 to achieve the same median survival.Conclusion: Replacing Glu in the PSMA-targeting Lys-urea-Glu pharmacophore of [68Ga]Ga-HTK03041 with Asp and Aad generates [68Ga]Ga-HTK03161 and [68Ga]Ga-HTK03149, respectively, and the new derivatives retain high uptake in LNCaP tumors and have minimal uptake in normal organs/tissues including kidneys and salivary glands. [177Lu]Lu-HTK03149 also retain high uptake in LNCaP tumors and has minimal uptake in normal organs/tissues, and is, therefore, promising for clinical translation to treat prostate cancer.

CXCR4-Directed PET/CT with [68Ga]Pentixafor in Central Nervous System Lymphoma: A Comparison with [18F]FDG PET/CT.

This study aimed to evaluate the value of [68Ga]Pentixafor PET/CT for the detection of lesions in central nervous system lymphoma (CNSL) patients before chemotherapy, during treatment and suspected CSNL recurrence, compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). Twenty-six patients with newly or previously diagnosed CNSL who underwent [68Ga]Pentixafor PET/CT were included retrospectively. Histopathological results, magnetic resonance imaging (MRI), and follow-up were used as the standard reference. The accuracy of lesion detection, maximum standardized uptake value (SUVmax) of tumors, and ratio of tumor-to-normal brain (T/N) with [68Ga]Pentixafor PET/CT were calculated and compared to those obtained with [18F]FDG PET/CT. CXCR4 expression was analyzed through immunohistochemistry. Of 26 patients, 18 were newly diagnosed with a total of 23 lesions, 4 had recurrent with 4 lesions, and 4 underwent a mid-term treatment assessment after 4 cycles of chemotherapy (3 achieved complete response (CR), 1 experienced progressive disease (PD) with a total of 8 lesions). Thirty-five lesions were all clearly detected with favorable contrast by [68Ga]Pentixafor PET/CT (accuracy, 100%), consistent with the results of contrast-enhanced magnetic resonance imaging (CE-MRI). The SUVmax of positive lesions in [68Ga]Pentixafor PET/CT was correlated with tumor size (r = 0.555, P = 0.001). In 21 patients, compared with [18F]FDG PET/CT, [68Ga]Pentixafor PET/CT showed a remarkably higher T/N ratio (21.93 ± 10.77 vs 4.29 ± 2.16, P = 0.000) and detected 5 more lesions in the mid-term treatment assessment of patients (P = 0.026). The CXCR4 expression of CNSL lesions was correlated with SUVmax of [68Ga]Pentixafor PET/CT (r = 0.772, P = 0.000). CXCR4-directed PET/CT using [68Ga]Pentixafor, with excellent tumor-to-background contrast, might be a more promising agent for the detection of lesions in CNSL patients than [18F]FDG PET/CT.

Correlation of 4'-[methyl-11C]-thiothymidine PET with Ki-67 immunohistochemistry separately in patients with newly diagnosed and recurrent gliomas.

4'-[methyl-11C]-thiothymidine (4DST) uptake on PET was correlated with proliferative activity separately in patients with newly diagnosed and recurrent gliomas. A total of 29 patients, 18 with newly diagnosed gliomas and 11 with recurrent gliomas who underwent 4DST PET/computed tomography (CT) were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) of tumor (T) and the mean SUV of normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) and total lesion proliferation (TLP) were also calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with 4DST PET parameters. All gliomas but three newly diagnosed gliomas had 4DST uptake on PET. No significant differences in SUVmax, T/N ratio, PTV, or TLP were observed between the newly diagnosed and recurrent gliomas. In the former, correlations between SUVmax (r = 0.57, P = 0.02), T/N ratio (r = 0.51, P = 0.03), PTV (r = 0.74, P < 0.001), and TLP (r = 0.76, P < 0.001) and the Ki-67 index were found. In the latter, the results did not seem to suggest any correlations between any of the PET parameters and Ki-67 index. Although preliminary, these results suggest that 4DST PET may be useful for the noninvasive evaluation of proliferation in patients with newly diagnosed gliomas. These data in a small recurrent patient population do not support a clear-cut correlation between 4DST uptake and proliferation.

Maximum standardized uptake value of the primary tumor does not improve candidate selection for sublobar resection

ObjectiveThis retrospective study examined whether adding the maximum standardized uptake value of a primary tumor to the consolidation-to-tumor ratio from a high-resolution computed tomography scan can improve the predictive accuracy for pathological noninvasive lung cancer and lead to better patient selection for sublobar resection. MethodsWe included 926 patients with clinical stage IA non–small cell lung cancer. Pathological noninvasive cancer (n = 515) was defined as any case without lymphatic invasion, vascular invasion, or lymph node metastasis. The prediction accuracies of maximum standardized uptake value and consolidation-to-tumor ratio were evaluated using receiver operating characteristic curves and area under the curve. ResultsFor consolidation-to-tumor ratio or maximum standardized uptake value alone, the area under the curves were 0.733 (95% confidence interval, 0.708-0.758) and 0.842 (95% confidence interval, 0.816-0.866), respectively. When the consolidation-to-tumor ratio and maximum standardized uptake value were combined, the area under the curve was 0.854 (95% confidence interval, 0.829-0.876). However, to obtain a predictive specificity of 97%, sensitivity needed to be 42.5% for the consolidation-to-tumor ratio, 38.3% for the maximum standardized uptake value, and 45.0% for these 2 in combination. ConclusionsOur results suggest that despite the high area under the curve for maximum standardized uptake value, caution is needed when using maximum standardized uptake value to select candidates for sublobar resection. We found that a low maximum standardized uptake value did not mean the tumor was a pathological noninvasive lung cancer. Therefore, using consolidation-to-tumor ratios from high-resolution computed tomography to decide whether sublobar resection is appropriate for patients with clinical stage IA non–small cell lung cancer is better than using maximum standardized uptake value when setting specificity to a conservative 97% for predicting pathological noninvasive lung cancer.

Pretreatment 18F-FDG PET/CT Imaging Predicts the KRAS/NRAS/BRAF Gene Mutational Status in Colorectal Cancer.

Objective To investigate the association between KRAS/NRAS/BRAF mutations and metabolic parameters of pretreatment 18F-FDG PET/CT in colorectal cancer (CRC). Methods A total of 85 patients with CRC were included in the study. PET/CT was performed in all the patients before surgery. The histopathological examination and analysis of the gene mutational status of the primary tumor were conducted. The associations among clinical features, PET metabolic parameters, and the gene mutational status were investigated. Moreover, receiver operating characteristic (ROC) curves for maximum standard uptake value (SUVmax) of the primary tumor were generated along with analysis of the target tissue to nontarget tissue ratio (T/NT) for predicting the efficacy of KRAS/NRAS/BRAF mutations in CRC. Finally, the corresponding area under the curve, the optimal cutoff value, and the corresponding sensitivity and specificity were obtained. Results The mutation rate of KRAS/NRAS/BRAF was 54.12% (46/85). In addition, both SUVmax and T/NT were significantly higher in the KRAS/NRAS/BRAF-mutation groups compared to the wild-type group (15.88 ± 6.71 vs. 12.59 ± 5.79, 8.04 ± 3.03 vs. 6.38 ± 2.80; P=0.012 and 0.004, respectively). Results from the ROC curve also showed that the cutoff values for T/NT and SUVmax were 5.14 and 12.40, respectively, while the predictive accuracy was 0.682 and 0.647, respectively. On the other hand, the sensitivity was 91.30% and 65.22% while the specificity was 43.59% and 64.10%, respectively. Moreover, univariate analysis showed that the KRAS/NRAS/BRAF mutation was not significantly associated with gender, age, lesion location, tumor length, pathological type, tissue differentiation, and UICC staging (all P > 0.05). Conclusion T/NT ratio and SUVmax could be the potential surrogate imaging indicators to predict the KRAS/NRAS/BRAF mutational status in CRC patients.

Correlación entre la captación de 18F-FDG del tumor primario con los factores pronósticos y subtipo molecular del cáncer ductal de mama

ObjectivesIn this study, we aimed to investigate the correlation between SUVmax of primary tumor and prognostic factors/molecular subtype in ductal breast cancer patients. Materials and methodsWe retrospectively reviewed 150 female patients with pathologically proven invasive ductal breast cancer from January 2015 to October 2019 who underwent 18F-FDG PET/CT for initial staging. Histopathological prognostic features of the primary tumor (histological grade, hormone receptor status, Ki-67 index, vb.) were obtained from the tru-cut biopsy report. In 18F-FDG PET/CT studies, the maximum standardized uptake value (SUVmax) of the primary breast tumor was calculated and compared with the presence of axillary lymphadenopathy and/or distant metastases, histopathological prognostic factors and molecular subtype. ResultsThe high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: high tumor size, high histologic grade, high Ki-67 index, axillary lymph node positivity and distant metastasis. SUVmax value was significantly higher in patients with basal subtype than patients with Luminal A subtype (8.14 ± 3.71 and 4.64 ± 2.45, p = 0.002). Correlation analysis revealed a low correlation between Ki-67 index and SUVmax (r = 0.276, p = 0.001) and moderate correlation between tumor size and SUVmax (r = 0.470, p = 0.001). In multivariate linear regression analysis, Ki-67 index and tumor size had a statistically significant effect on SUVmax values. As these parameters increase, it is seen that it increases SUVmax values (p = 0.004, Std Beta: 0.228, 95% CI: 0.010–0.055 and p = 0.001, Std Beta: 0.374, 95% CI: 0.55–0.136, respectively). ConclusiónHigh SUVmax value is associated with prognotic factors suggesting poor prognosis. Pretreatment 18F-FDG PET/CT can be used as a tool to predict prognosis in breast cancer.

Efficacy of positron emission tomography in diagnosis of lateral lymph node metastases in patients with rectal Cancer: a retrospective study

BackgroundThe presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis.MethodsEighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination.ResultsOf the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity.ConclusionsThe cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Prognostic value of pretreatment F-18 fluorodeoxyglucose PET/CT in colorectal cancer with unresectable metastasis.

The aim of the study was to assess the prognostic value of pretreatment PET/computed tomography (CT) scans in colorectal cancer (CRC) patients with unresectable metastasis. We retrospectively reviewed the pretreatment PET/CT images of 82 CRC patients with unresectable metastasis and their medical records. On PET/CT images, maximum standardized uptake value (SUVmax) of primary tumor, highest SUVmax of metastatic tumors and number of metastatic organs were identified. The patients were further divided into single and multiple organ metastases groups according to the extent of disease. Survival analysis was performed with the clinical variables and metabolic parameters from PET/CT. In a total of 82 patients, the age of patients, highest SUVmax of metastatic tumors and number of metastatic organs were independent prognostic factors for overall survival (OS) (all P < 0.05), whereas the SUVmax of primary tumor was not. On multivariate analysis, only the SUVmax of metastatic tumor was a significant prognostic factor in the single organ metastasis group (P = 0.047), whereas the age and highest SUVmax of metastatic tumors were independent prognostic factors in the multiple organ metastases group (all P < 0.05). The highest SUVmax of metastatic tumors was an independent prognostic factor for OS in CRC patients with unresectable metastasis.

Relationships of 18F-FDG uptake by primary tumors with prognostic factors and molecular subtype in ductal breast cancer

ObjectivesIn this study, we aimed to investigate the correlation between SUVmax of primary tumor and prognostic factors/molecular subtype in ductal breast cancer patients. Materials and methodsWe retrospectively reviewed 150 female patients with pathologically proven invasive ductal breast cancer from January 2015 to October 2019 who underwent 18F-FDG PET/CT for initial staging. Histopathological prognostic features of the primary tumor (histological grade, hormone receptor status, Ki-67 index, vb.) were obtained from the tru-cut biopsy report. In 18F-FDG PET/CT studies, the maximum standardized uptake value (SUVmax) of the primary breast tumor was calculated and compared with the presence of axillary lymphadenopathy and/or distant metastases, histopathological prognostic factors and molecular subtype. ResultsThe high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: high tumor size, high histologic grade, high Ki-67 index, axillary lymph node positivity and distant metastasis. SUVmax value was significantly higher in patients with basal subtype than patients with Luminal A subtype (8,14 ± 3,71 and 4,64 ± 2,45, p = 0,002). Correlation analysis revealed a low correlation between Ki-67 index and SUVmax (r = 0,276, p = 0,001) and moderate correlation between tumor size and SUVmax (r = 0,470, p = 0,001). In multivariate linear regression analysis, Ki-67 index and tumor size had a statistically significant effect on SUVmax values. As these parameters increase, it is seen that it increases SUVmax values (p = 0,004, Std Beta: 0,228, 95% CI:0,010–0,055 and p = 0,001, Std Beta:0,374, 95% CI:0,55–0,136, respectively). ConclusionHigh SUVmax value is associated with factors suggesting poor prognosis. Pretreatment 18F-FDG PET/CT can be used as a tool to predict prognosis in breast cancer.

Positron Emission Tomography in Segmentectomy for cT1N0M0 Nonsmall Cell Lung Cancer.

This study was aimed to examine the significance of fluorodeoxyglucose positron emission tomography in predicting prognosis after segmentectomy in lung cancer. This was a retrospective cohort study, including 227 patients with cT1N0M0 nonsmall cell lung cancer who underwent positron emission tomography followed by segmentectomy between 2012 and 2019. Significance of tumor histology, T-stage, tumor size, and standardized uptake value on positron emission tomography in relation to recurrence-free survival were examined using Cox's proportional hazard analysis. Median follow-up period was 56 months (range: 1-95 months). Tumor stages were Tis in 25 patients, T1mi/T1a in 51, T1b in 98, and T1c in 53. Twenty-six patients (11%) experienced recurrences, including local (n = 8) and distant (n = 18). Multivariate analysis showed that the significant variables for recurrence-free survival were T-stage and standardized uptake value (p = 0.002 and 0.015, respectively), whereas tumor histology and tumor size were not significant (p = 0.28 and 0.44, respectively). When tumor size was divided into ≤2 cm and >2 cm for analysis, it was not significant again (p = 0.49), whereas standardized uptake value remained significant (p = 0.008). While standardized uptake value of tumors with recurrences was significantly higher than those without (4.9-2.8 and 2.6-2.5, respectively, p < 0.001), there was no significant difference between local and distant recurrences (p = 0.32). Cut-off value of standardized uptake value for recurrences was 3.2. Five-year recurrence-free survival rates in tumors with standardized uptake value <3.2 and ≥3.2 were 86 and 65%, respectively (p < 0.001). Positron emission tomography could predict the prognosis after segmentectomy better than tumor size.