Quantitative evaluation of PSMA PET imaging using a realistic anthropomorphic phantom and shell-less radioactive epoxy lesions

Background Positron emission tomography (PET) with prostate specific membrane antigen (PSMA) have shown superior performance in detecting metastatic prostate cancers. Relative to [18F]fluorodeoxyglucose ([18F]FDG) PET images, PSMA PET images tend to visualize significantly higher-contrast focal lesions. We aim to evaluate segmentation and reconstruction algorithms in this emerging context. Specifically, Bayesian or maximum a posteriori (MAP) image reconstruction, compared to standard ordered subsets expectation maximization (OSEM) reconstruction, has received significant interest for its potential to reach convergence with minimal noise amplifications. However, few phantom studies have evaluated the quantitative accuracy of such reconstructions for high contrast, small lesions (sub-10 mm) that are typically observed in PSMA images. In this study, we cast 3 mm–16-mm spheres using epoxy resin infused with a long half-life positron emitter (sodium-22; 22Na) to simulate prostate cancer metastasis. The anthropomorphic Probe-IQ phantom, which features a liver, bladder, lungs, and ureters, was used to model relevant anatomy. Dynamic PET acquisitions were acquired and images were reconstructed with OSEM (varying subsets and iterations) and BSREM (varying β parameters), and the effects on lesion quantitation were evaluated. Results The 22Na lesions were scanned against an aqueous solution containing fluorine-18 (18F) as the background. Regions-of-interest were drawn with MIM Software using 40% fixed threshold (40% FT) and a gradient segmentation algorithm (MIM’s PET Edge+). Recovery coefficients (RCs) (max, mean, peak, and newly defined “apex”), metabolic tumour volume (MTV), and total tumour uptake (TTU) were calculated for each sphere. SUVpeak and SUVapex had the most consistent RCs for different lesion-to-background ratios and reconstruction parameters. The gradient-based segmentation algorithm was more accurate than 40% FT for determining MTV and TTU, particularly for lesions $$\le$$ ≤ 6 mm in diameter (R2 = 0.979–0.996 vs. R2 = 0.115–0.527, respectively). Conclusion An anthropomorphic phantom was used to evaluate quantitation for PSMA PET imaging of metastatic prostate cancer lesions. BSREM with β = 200–400 and OSEM with 2–5 iterations resulted in the most accurate and robust measurements of SUVmean, MTV, and TTU for imaging conditions in 18F-PSMA PET/CT images. SUVapex, a hybrid metric of SUVmax and SUVpeak, was proposed for robust, accurate, and segmentation-free quantitation of lesions for PSMA PET.

Metabolic Tumour Volume as a Predictor of Survival for Sinonasal Tract Squamous Cell Carcinoma

Background: High uptake of F18-fluorodeoxyglucose parameters for glucose metabolism is related to shorter survival in sinonasal tract cancer with various histological classifications. We investigated whether F18-fluorodeoxyglucose uptake parameters are associated with survival outcomes for patients with only squamous cell carcinoma (SCC) in the sinonasal tract that are treated either with surgery or nonsurgery. Methods: We retrospectively observed F18-fluorodeoxyglucose uptake parameters on positron emission tomography with computed tomography for the primary tumour of SCC in 39 patients. Log-rank test or a Cox regression model with 95% confidence interval (95%CI) and hazard ratio (HR) were used for monovariable or multivariable analysis, respectively. We determined cut-off values of the F18-fluorodeoxyglucose uptake parameters using the lowest p value for monovariable sinonasal tract cancer-specific survival analysis. Results: Monovariable analysis showed that patients with metabolic tumour volume (MTV) ≥ 21.8 had a shorter cancer-specific, disease-free and local recurrence-free survival than those with MTV < 21.8. After adjusting for age, gender, clinical stage and treatment group in the multivariable analysis, MTV (≥21.8/<21.8) was related to shorter cancer-specific (HR: 3.69, 95%CI: 1.17–12.0), disease-free (HR: 3.38, 95%CI: 1.19–9.71) and local recurrence-free (HR: 5.42, 95%CI: 1.59–20.3) survivals. Conclusions: MTV as advances in diagnostics of sinonasal tract SCC is a predictor.

Metabolic Activity Via 18 F-FDG PET/CT is Predictive of Microsatellite Instability Status In Colorectal Cancer

Purpose: Identification of microsatellite instability high (MSI-H) colorectal cancer (CRC) is crucial for screening patients most likely to benefit from immunotherapy. We aim to investigate whether the metabolic characteristics is related to MSI status and can be used to predict the MSI-H CRC. Methods: A retrospective analysis was conducted on 420 CRC patients who were identified via [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography(CT) prior to therapy. Maximum standardised uptake (SUVmax), mean standardised uptake (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were calculated and compared between MSI-H and microsatellite stability (MSS). Predictive factors of MSI status were selected from metabolic parameters and clinicopathological profiles via a multivariate analysis.Results: Of 420 colorectal cancers, 44 exhibited a high incidence of MSI. Both MTV and TLG were significantly higher in MSI-H group compared with the MSS group (P=0.004 and P=0.010, respectively). Logistic regression analysis indicated that CRC with MSI-H were related to younger age (P=0.013), primary lesion located at right hemi-colon (P<0.001) and larger MTV on PET/CT imaging (P=0.019). MTV more than 32.19 cm3 of colorectal cancer was linked to the presence of MSI (P=0.019). Conclusion: Tumor metabolic burden were higher in MSI-H CRC which may be useful for predicting the MSI status of CRC patient and thus aid in determination of immunotherapy for patients with CRC.

Prognostic value of baseline metabolic tumour volume in advanced-stage Hodgkin’s lymphoma

Our aim was to evaluate the prognostic value of initial total metabolic tumour volume (TMTV) in a population of patients with advanced-stage Hodgkin’s lymphoma (HL). We retrospectively included 179 patients with stage IIb-III-IV Hodgkin’s disease who received BEACOPP or ABVD as the first-line treatment. The initial TMTV was determined using a semi-automatic method for each patient. We analysed its prognostic value in terms of 5-year progression-free survival (PFS), overall survival, and positron emission tomography (PET) response after two courses of chemotherapy. Considering all the treatments and using a threshold of 217 cm3, TMTV was predictive of 5-year PFS and PET response after two courses of chemotherapy. In multivariable analysis involving TMTV, IPI score, and the first treatment received, TMTV remained a baseline prognostic factor for 5-year PFS. In the subgroup of patients treated with BEACOPP with a threshold of 331 cm3, TMTV was predictive of PET response, but not 5-year PFS (p = 0.087). The combined analysis of TMTV and PET response enabled the individualisation of a subgroup of patients (low TMTV and complete response on PET) with a very low risk of recurrence. Baseline TMTV appears to be a useful independent prognostic factor for predicting relapse in advanced-stage HL in ABVD subgroup, with a tendency of survival curves separation in BEACOPP subgroup.

Metabolic tumour volume on 18F-FDG PET/CT predicts extended pathological T stages in patients with renal cell carcinoma at staging

We evaluated the predictive value of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/CT (PET/CT) for extended pathological T (pT) stages (≥ pT3a) in Renal cell carcinoma (RCC) patients at staging. Thirty-eight RCC patients who underwent 18F-FDG PET/CT at staging, followed by radical nephrectomy between September 2016 and September 2018, were included in this prospective study. Patients were classified into two groups (limited pT stage: stage T1/2, n = 17; extended pT stage: T3/4, n = 21). Univariate and multivariate logistic regression analyses were performed to identify clinicopathological and metabolic variables to predict extended pT stages. 18F-FDG metabolic parameters were compared in relation to International Society of Urological Pathology (ISUP) grade and lymphovascular invasion (LVI). In univariate analysis, maximum standardised uptake value, metabolic tumour volume (MTV), and ISUP grade were significant. In multivariate analysis, MTV was the only significant factor of extended pT stages. With a cut-off MTV of 21.2, an area under the curve was 0.944, which was higher than 0.824 for clinical T stages (p = 0.037). In addition, high MTV, but not tumour size, was significantly correlated with aggressive pathologic features (ISUP grade and LVI). High glycolytic tumour volume on 18F-FDG PET/CT in RCC patients at staging is predictive of extended pT stages which could aid decision-making regarding the best type of surgery.

Quantitative Evaluation of PSMA PET Imaging using a Realistic Anthropomorphic Phantom and Shell-less Radioactive Epoxy Lesions

Background Prostate specific membrane antigen (PSMA) PET images have shown superior performance in detecting metastatic prostate cancers. Relative to [18F]FDG PET images, PSMA PET images tend to visualize significantly higher-contrast focal lesions. We aim to evaluate segmentation and reconstruction algorithms in this emerging context. Specifically, Bayesian or maximum a posteriori (MAP) image reconstruction, compared to standard OSEM reconstruction, has received significant interest for its potential to reach convergence with minimal noise amplifications. However, few phantom studies have evaluated the quantitative accuracy of such reconstructions for high contrast, small lesions (sub-10mm) that are typically observed in PSMA images. In this study, we cast 3mm-16mm spheres using epoxy resin infused with a long half-life positron emitter (sodium-22; 22Na) to simulate prostate cancer metastasis. The anthropomorphic Probe-IQ phantom, which features a liver, bladder, lungs, and ureters, was used to model relevant anatomy. Dynamic PET acquisitions were acquired and images were reconstructed with OSEM (varying subsets and iterations) and BSREM (varying β parameters), and the effects on lesion quantitation were evaluated. Results The 22Na lesions were scanned against an aqueous solution containing fluorine-18 (18F) as the background. Due to the long half-life of 22Na compared to 18F, a separate scan with fully-decayed background was used to measure the ground truth radioactivity concentrations of the 22Na lesions. Regions-of-interest were drawn with MIM Software using 40% fixed threshold (40% FT) and a gradient segmentation algorithm (MIM’s PET Edge+). Recovery coefficients (RCs) (max, mean, peak, and newly defined “apex”) and metabolic tumour volume (MTV) were calculated for each sphere. SUVpeak and SUVapex had the most consistent RCs for different lesion-to-background ratios and reconstruction parameters. The gradient-based segmentation algorithm was more accurate than 40% FT for determining MTV, particularly for lesions \(\le\)6mm in diameter (R2 = 0.86–0.89 vs. R2 < 0.02, respectively). Conclusion An anthropomorphic phantom was used to evaluate quantitation for PSMA PET imaging of metastatic prostate cancer lesions. BSREM with β = 200–400 and OSEM with 1–2 iterations resulted in the most accurate SUV and MTV values for these imaging conditions. SUVapex, a hybrid metric of SUVmax and SUVpeak, was proposed for robust, accurate, and segmentation-free quantitation of lesions for PSMA PET.

Prognostic value of baseline total metabolic tumour volume of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma

Purpose The aim of this study was to explore the prognostic value of baseline metabolic parameters of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma (AITL). Materials and methods Fifty-six AITL patients (average age 64.0 ± 1.3 years) diagnosed pathologically from August 2009 to August 2019 were enrolled in this retrospective study. The total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax), and correlated clinical characteristics were collected and analysed. TMTV was computed with the 41% SUVmax threshold method. The chi-square test or Fisher’s exact probability method was used to compare clinical characteristics. Kaplan–Meier curves were used to describe progression-free survival (PFS) and overall survival (OS). The log-rank test was used to analyse the difference within groups. The statistically significant factors in the univariate regression analysis were incorporated into the Cox risk proportional regression model for multivariate survival analysis. Results The TMTV cut-off value was 514.6 cm3 from the ROC curve analysis. Forty (71.4%) patients progressed and 31 (55.4%) patients died within a median follow-up time of 19.1 (interquartile range 7.8–34.6) months. The 1-year and 3-year PFS rates were 42.9% and 30.1%, and the 3-year and 5-year OS rates were 45.9% and 34.4%, respectively. Univariate survival analysis showed that high TMTV and TLG may be the factors contributing to poor PFS and OS. Multivariate analysis showed that TMTV and prognostic index for T-cell lymphoma (PIT) were independent parameters for PFS and OS in AITL patients. TMTV, combined with PIT, may have better risk stratification performance than TMTV alone. Conclusions Baseline TMTV and PIT were independent prognostic predictors in AITL patients. The combination of TMTV and PIT can facilitate prognostic stratification and contribute to personalized therapy.

11C-methyl-L-methionine PET measuring parameters for the diagnosis of tumour progression against radiation-induced changes in brain metastases

Objectives: Radiation-induced changes (RIC) secondary to focal radiotherapy can imitate tumour progression in brain metastases and make follow-up clinical decision making unreliable. 11C-methyl-L-methionine-PET (MET-PET) is widely used for the diagnosis of RIC in brain metastases, but minimal literature exists regarding the optimum PET measuring parameter to be used. We analysed the diagnostic performance of different MET-PET measuring parameters in distinguishing between RIC and tumour progression in a retrospective cohort of brain metastasis patients. Methods: 26 patients with 31 metastatic lesions were included on the basis of having undergone a PET scan due to radiological uncertainty of disease progression. The PET images were analysed and methionine uptake quantified using standardised-uptake-values (SUV) and tumour-to-normal tissue (T/N) ratios, generated as SUVmean, SUVmax, SUVpeak, T/Nmean, T/Nmax-mean and T/Npeak-mean. Metabolic-tumour-volume and total-lesion methionine metabolism were also computed. A definitive diagnosis of either RIC or tumour progression was established by clinicoradiological follow-up of least 4 months subsequent to the investigative PET scan. Results: All MET-PET parameters except metabolic-tumour-volume showed statistically significant differences between tumour progression and lesions with RIC. Receiver-operating-characteristic curve and area-under the-curve analysis demonstrated the highest value of 0.834 for SUVmax with a corresponding optimum threshold of 3.29. This associated with sensitivity, specificity, positive predictive and negative predictive values of 78.57, 70.59%, 74.32 and 75.25% respectively. Conclusions: MET-PET is a useful modality for the diagnosis of RIC in brain metastases. SUVmax was the PET parameter with the greatest diagnostic performance. Advances in knowledge: More robust comparisons between SUVmax and SUVpeak could enhance follow-up treatment planning.