Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by ¹⁸F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

We performed a systematic evaluation of the diagnostic performance of LAFOV PET/CT with increasing acquisition time. The first 100 oncologic adult patients referred for 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose PET/CT on the Siemens Biograph Vision Quadra were included. A standard imaging protocol of 10 min was used and scans were reconstructed at 30 s, 60 s, 90 s, 180 s, 300 s, and 600 s. Paired comparisons of quantitative image noise, qualitative image quality, lesion detection, and lesion classification were performed. Image noise (n = 50, 34 women) was acceptable according to the current standard of care (coefficient-of-variance_ref < 0.15) after 90 s and improved significantly with increasing acquisition time (P_B < 0.001). The same was seen in observer rankings (P_B < 0.001). Lesion detection (n = 100, 74 women) improved significantly from 30 s to 90 s (P_B < 0.001), 90 s to 180 s (P_B = 0.001), and 90 s to 300 s (P_B = 0.002), while lesion classification improved from 90 s to 180 s (P_B < 0.001), 180 s to 300 s (P_B = 0.021), and 90 s to 300 s (P_B < 0.001). We observed improved image quality, lesion detection, and lesion classification with increasing acquisition time while maintaining a total scan time of less than 5 min, which demonstrates a potential clinical benefit. Based on these results we recommend a standard imaging acquisition protocol for LAFOV PET/CT of minimum 180 s to maximum 300 s after injection of 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose.

The aim of this Phase II study was to investigate the potential for response assessment and prognostication of positron emission tomography (PET) using the ligand ⁶⁸Ga-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) in patients receiving Radium-223-dichloride therapy (²²³RaCl₂). A combined whole-body uPAR PET and computed tomography (CT) was performed before initiation of ²²³RaCl₂ and after two cycles of therapy. Standardized uptake value (SUV) in selected bone metastases was measured and the lesion with the highest SUV_max was considered the index lesion. Clinical outcomes were overall survival (OS), radiographic progression free survival (rPFS) and occurrence of symptomatic skeletal event (SSE). A total of 17 patients were included and 14 patients completed both baseline and follow-up uPAR-PET/CT. Baseline SUV_max of the index lesion was associated with OS; hazard ratio 2.51 (95% CI: 1.01–6.28, p = 0.05) per unit increase in SUV_max. No association between changes in SUV_max from baseline to follow-up and OS, progression during therapy, or rPFS was found. Baseline SUV_max was a significant predictor of SSE with receiver operating characteristics (ROC) area under the curve (AUC) = 0.81 (95% CI: 0.58–1.00, p = 0.034). A cut-off for tumor SUV_max could be established with an odds ratio of 14.0 (95% CI: 1.14–172.6, p = 0.023) for occurrence of SSE within 12 months. Although based on a small number of patients, uPAR-PET SUV_max in bone metastases was predictive for OS and risk of SSE in mCRPC patients receiving ²²³RaCl₂. However, a relatively low uptake of the uPAR ligand in bone metastases impedes visual evaluation and requires another modality for lesion delineation.

Arginine-Glycine-Aspartate (RGD)-recognizing cell surface integrins are involved in tumor growth, invasiveness/metastases, and angiogenesis, and are therefore an attractive treatment target in cancers. The subtype integrin α_vβ₃ is upregulated on endothelial cells during angiogenesis and on tumor cells. In vivo assessment of integrin α_vβ₃ is possible with positron emission tomography (PET). Preclinical data on radiochemical properties, tumor uptake and radiation exposure identified [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ as a promising candidate for clinical translation. In this first-in-human phase I study, we evaluate [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ PET in patients with neuroendocrine neoplasms (NEN) and breast cancer (BC). The aim was to investigate safety, biodistribution and dosimetry as well as tracer uptake in tumor lesions. A total of 10 patients (5 breast cancer, 5 neuroendocrine neoplasm) received a single intravenous dose of approximately 200 MBq [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂. Biodistribution profile and dosimetry were assessed by whole-body PET/CT performed at 10 min, 1 h and 2 h after injection. Safety assessment with vital parameters, electrocardiograms and blood tests were performed before and after injection. In vivo stability of [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ was determined by analysis of blood and urine. PET images were analyzed for tracer uptake in tumors and background organs. No adverse events or pharmacologic effects were observed in the 10 patients. [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ exhibited good in vivo stability and fast clearance, primarily by renal excretion. The effective dose was 0.022 mSv/MBq, equaling a radiation exposure of 4.4 mSv at an injected activity of 200 MBq. The tracer demonstrated stable tumor retention and good image contrast. In conclusion, this first-in-human phase I trial demonstrated safe use of [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ for integrin α_vβ₃ imaging in cancer patients, low radiation exposure and favorable uptake in tumors. Further studies are warranted to establish whether [⁶⁸Ga]Ga-NODAGA-E[c(RGDyK)]₂ may become a tool for early identification of patients eligible for treatments targeting integrin α_vβ₃ and for risk stratification of patients.

Background: Total body and long-axial field-of-view (LAFOV) PET/CT represent visionary innovations in imaging enabling either improved image quality, reduction in injected activity–dose or decreased acquisition time. An improved image quality may affect visual scoring systems, including the Deauville score (DS), which is used for clinical assessment of patients with lymphoma. The DS compares SUVmax in residual lymphomas with liver parenchyma, and here we investigate the impact of reduced image noise on the DS in patients with lymphomas scanned on a LAFOV PET/CT. Methods: Sixty-eight patients with lymphoma underwent a whole-body scan on a Biograph Vision Quadra PET/CT-scanner, and images were evaluated visually with regard to DS for three different timeframes of 90, 300, and 600 s. SUVmax and SUVmean were calculated from liver and mediastinal blood pool, in addition to SUVmax from residual lymphomas and measures of noise. Results: SUVmax in liver and in mediastinal blood pool decreased significantly with increasing acquisition time, whereas SUVmean remained stable. In residual tumor, SUVmax was stable during different acquisition times. As a result, the DS was subject to change in three patients. Conclusions: Attention should be drawn towards the eventual impact of improvements in image quality on visual scoring systems such as the DS.