RPS 1906 - Moving molecular imaging forward: experimental and beyond oncology

Author Block: M. J. Antons, F. Herr, M. Heimer, S. Lindner, M. Brendel, D-A. Clevert, J. Ricke, R. Werner, C. C. Cyran; Munich/DE
Purpose: While immune checkpoint inhibitors have demonstrated considerable efficacy in malignant melanoma, interindividual variability necessitates robust imaging biomarkers for response evaluation. This study compared the diagnostic performance of [18F]FDG-PET/CT, multiparametric MRI and contrast-enhanced ultrasound (CEUS) in monitoring the effects of a combined anti-PD-L1/anti-CTLA-4-immunotherapy in a murine melanoma model with immunohistochemical validation.
Methods or Background: C57BL/6 mice (female, n=88) were inoculated subcutaneously with B16-F10 melanoma cells into the left abdominal flank and randomized into therapy and control groups. The therapy group received intraperitoneal injections of anti-PD-L1- and anti-CTLA-4-antibodies, while the control group received sham treatment. Imaging assessments at baseline (day 7 post inculation), follow-up 1 (FU-1; day 13) and follow-up 2 (FU-2; day 19) included [18F]FDG-PET/CT (n=40), multiparametric MRI (n=28) and CEUS (n=20). Tumor allografts were harvested for ex vivo immunohistochemical validation (CD8, Ki-67, TUNEL, CD31).
Results or Findings: [18F]FDG-PET/CT revealed significantly lower MTV and SUVmax in the therapy group (FU-1: MTV: p=0.004; FU-2: MTV: p=0.008, SUVmax: p=0.0003). MRI demonstrated significantly lower ADC in the therapy group at follow-up (FU-1: p = 0.002). CEUS showed significant reduction in tumor perfusion (WiAUC, p=0.0152) and a significantly lower number of VEGFR2-targeted microbubbles in the therapy group (SI8min: p=0.003; SI10min: p=0.0019). Immunohistochemistry confirmed significantly higher apoptosis rates (FU-1: p=0.012; FU-2: p=0.001), more CD8-positive T-cells (FU-2: p=0.003), lower tumor cell proliferation (FU-1: p=0.012; FU-2: p=0.012) and lower microvascular density (FU-1: CD31: p<0.001) in the therapy group.
Conclusion: This study highlights the complementary strengths of PET/CT, MRI, and CEUS in assessing immunotherapy response in malignant melanoma. [18F]FDG-PET/CT provided early metabolic response parameters, MRI parameters reflected cellular and microstructural tumor alterations and CEUS detected vascular remodelling.
Limitations: The observation period was relatively short and no clinical endpoints such as overall survival of the animals were determined.
Funding for this study: This work was supported by a research grant from Bracco Imaging SA, Geneva, Switzerland, which provided the BR55 free of charge.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information:

Author Block: F. Herr, S. Kloiber-Langhorst, M. M. Li, O. Dietrich, J. Ricke, C. C. Cyran, J. Andrassy; Munich/DE
Purpose: To assess the effect of cold ischemia duration on MRI-derived perfusion parameters in kidney transplants of mice after long-term post-transplant survival.
Methods or Background: Fifteen C57BL/6 mice underwent kidney transplantation and were divided into two groups based on cold ischemia time: 30 minutes (n = 6) and 16 hours (n = 9). Dynamic contrast-enhanced MRI was performed at a mean of 268 ± 29.9 days post-transplantation. Perfusion parameters were calculated using the Patlak model, yielding the plasma volume fraction (vp), representing blood volume/perfusion, and the volume transfer constant (Ktrans), reflecting vascular permeability. Intergroup comparisons were performed using the Mann–Whitney U-test.
Results or Findings: Significant differences were observed in the Ktrans parameter of transplanted kidneys between the ischemia groups. The median Ktrans was significantly elevated in the 16 h group (2.82 ± 0.47 mL/100 mL/min) versus the 1 h group (1.16 ± 0.53 mL/100 mL/min; p = 0.008). In contrast, vp did not differ significantly between the groups. Median vp was 20.56 ± 7.02 mL/100 mL (16 h) versus 30.69 ± 8.11 mL/100 mL (1 h; p = 0.151). No significant differences were observed between the transplanted kidney and the contralateral native kidneys for any of the Patlak-derived parameters.
Conclusion: Prolonged cold ischemia of 16 hours leads to significantly increased Ktrans values in murine kidney transplants, indicating impaired microvascular integrity after long-term engraftment. These finding suggest that cold ischemia duration may be a critical factor influencing graft microcirculation even in the chronic post-transplant phase.
Limitations: The study includes a relatively small sample size, which limits statistical power. Additionally, potential interindividual anatomical variations in the small mouse kidneys could influence quantification; however, we largely counteracted this through standardized ROI placements and modeling.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the government of Upper Bavaria (ROB-55.2-2532.Vet_02-20-186) and carried out in accordance to the EU Directive 2010/63 for the protection of animals used for scientific purposes and was reported in compliance to ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines.

Author Block: J. Dai, X-G. Peng; Nanjing/CN
Purpose: Pancreatic tumor therapy is severely hindered by chemotherapy resistance. Oxaliplatin (OXA) efficacy is limited by dual resistance mechanisms: glutathione (GSH)-mediated detoxification and lipid metabolic reprogramming. Although the metabolic hormone Irisin represents a potential strategy to modulate lipid metabolism, its systemic delivery raises concerns about potentially exacerbating cancer-associated cachexia. Furthermore, non-invasive methods to dynamically monitor metabolic changes and treatment response are critically needed.
Methods or Background: The platinum-palladium-rhodium-iron quaternary mesoporous nanozyme co-loaded with OXA and Irisin (PtPdRhFe@OXA/Irisin) was developed for the targeted co-delivery to pancreatic tumors in mice. This theranostic platform was assessed via a multi-modal imaging strategy: 1) Near-infrared fluorescence (NIRF) imaging for real-time tracking of tumor accumulation; 2) Serial MRI at weekly intervals to quantitatively monitor tumor volume changes and assess lipid content, providing a non-invasive measure of metabolic response.
Results or Findings: The nanosystem demonstrated effective CD44-targeted delivery to tumors, as confirmed by NIRF signals exclusively at the tumor site. Weekly MRI scans revealed that mice treated with PtPdRhFe@OXA/Irisin exhibited a significant suppression in tumor growth compared to control groups. MRI-based assessment indicated a notable decrease in intratumoral lipid content, suggesting Irisin affects pancreatic tumor lipid metabolic reprogramming in mice. This metabolic shift sensitized tumors to OXA, whose effect was further enhanced by the nanozyme's dual enzyme-mimetic activities, scavenging GSH and elevating ROS.
Conclusion: The multifunctional nanosystem PtPdRhFe@OXA/Irisin exerts potent anti-pancreatic tumor effects by targeting lipid metabolic reprogramming in synergy with GSH depletion and oxidative stress induction, while enabling non-invasive monitoring via multi-modal imaging.
Limitations: The precise molecular pathways by which Irisin reprograms lipid metabolism require further elucidation.
Funding for this study: National Natural Science Foundation of China (82272064)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The Institutional Animal Care and Use Committee of the Medical School of Southeast University (Approve ID: 20240226015)

Author Block: H. Abdul Razak¹, w. d. Strain¹, P. Rogers¹, M. Faghy², S. Kranen¹, K. Mokbel¹, M. Scott-Cleasby¹, J. Hoare¹, K. Knapp¹; ¹Exeter/UK, ²Derby/UK
Purpose: Long-COVID is a long-term sequela arising from an acute infection with SARS-CoV-2. To date there is no known cure. The ERASE feasibility trial will evaluate the efficacy of Remdesivir for the treatment of Long COVID with a wide range of outcome measures. This abstract outlines the nested parametric PET/CT study and the novel protocol utilised.
Methods or Background: Whole body (WB) 18F-FDG PET/CT scans were performed in 20 participants at one centre on day 11 for the baseline scan and day 55 for the follow-up scan with a maximum dose constraint of 31.2mSv for both scans, but a typical dose of 22mSv. Dynamic scans were acquired using the Siemens Motionflow acquisition on a Siemens Biograph Vision 600 scanner (Siemens, Germany) with an acquisition time of 75 to 90 minutes depending on the height of the participant. Patient public involvement and engagement was undertaken throughout the study design.
Results or Findings: The long scan duration was generally well tolerated by the participants. The image quality was diagnostic and both SUV and Ki were calculated for major organs and bone marrow, the latter using the automated Patlak algorithm in Siemens Syngo Via software (Siemens Healthineers, Germany).
Conclusion: In conclusion, this protocol demonstrates a novel use of parametric PET/CT 18F-FDG WB scans for the assessment of Long COVID and response to Remdesivir. The opportunity to quantify metabolic changes in a disease which has a range of presentations provides the potential to identify drug efficacy in different organs, which could provide useful insights for the future in both diagnosing and treating this disease.
Limitations: This study was performed at a single centre on a single scanner and further quantitative analysis of image quality and baseline to follow-up changes is required.
Funding for this study: This study was funded by Gilead Sciences
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: IRAS number: 1007101