RPS 2006 - Hybrid and molecular imaging in oncology: clinical and translational studies

Author Block: L. Kessler, B. M. Schaarschmidt, J. Siveke, L. Umutlu, M. Schuler, M. Stuschke, K. Herrmann, W. Fendler, H. Hautzel; Essen/DE
Purpose: Mesothelioma are rare tumors mostly affecting the pleura and are associated with overall poor prognosis. Mesothelioma subtypes have shown to express fibroblast-activation-protein (FAP) in tumor cells, suggesting FAP as a promising target for imaging and therapy. Thus, novel radiolabeled FAP-inhibitors (FAPI) are of interest for future theranostic approaches. The FAPI-PET observational trial (NCT04571086) evaluates Ga-68-FAPI PET imaging in cancer patients and here we present data on Ga-68-FAPI in patients with mesothelioma.
Methods or Background: Forty-one patients underwent Ga-68 FAPI-PET imaging and F-18-FDG PET. The primary endpoint was correlation of Ga-68-FAPI-PET uptake (SUVmax and SUVpeak) with histopathological FAP expression. Secondary objectives included detection rate and diagnostic performance (sensitivity, specificity, positive/negative predictive values and accuracy) compared to F-18-FDG PET validated by histopathology or a compound reference standard (histopathology, alternative imaging or follow-up imaging).
Results or Findings: SUVmax and SUVpeak values showed a significant correlation with histopathological FAP expression (SUVmax r = 0.49, p = 0.04; SUVpeak r = 0.51, p = 0.03). Overall Ga-68-FAPI showed high diagnostic performance (SE 98%, SP 81%, PPV 88% and NPV 97%). Ga-68-FAPI had similiar sensivity compared to F-18-FDG on both per-patient (100.0% vs. 97.3%) and per-region (98.0% vs. 95.9%) basis but showed increased Specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%) in per-region analysis, indicating superior performance. This discrepancy was attributed to a higher number of false positive regions on F-18-FDG (FAPI, N = 7 vs. FDG, N = 31).
Conclusion: This is the first study to show correlation between Ga-68-FAPI uptake and histopathological FAP expression and superior diagnostic value compared to F-18-FDG in mesothelioma patients. These findings highlight the potential of Ga-68-FAPI as a potential tool in clinical practice.
Limitations: The limitations are single center, observational cohort with heterogenous patients.
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: University Duisburg-Essen permits 19-8991-BO and 20-9485-BO

Author Block: T. Russo, C. Bezzi, C. Sabini, G. Candotti, G. Ironi, F. De Cobelli, P. Mapelli, A. Chiti, M. Picchio; Milan/IT
Purpose: This study aims at evaluating the effectiveness of fully hybrid [18F]FDG PET/MRI in EC staging, assessing its diagnostic accuracy and prognostic role in predicting features of EC aggressiveness, including p53abn MMRd for the new molecular classification.
Methods or Background: This prospective study involved 80 patients with biopsy-confirmed EC who underwent preoperative [18F]FDG PET/MRI for staging purposes. The PET/MRI scans were independently reviewed by a radiologist and a nuclear medicine physician, assessing the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive and negative predictive value (PPV, NPV). Imaging and clinical parameters were then investigated for their correlation (Spearman's rank correlation) and analyzed through Fisher’s exact test, and ROC analysis. Kaplan-Meier survival curves, Log-rank tests and Cox proportional hazards models were used to evaluate the prognostic value of parameters for predicting tumor relapse.
Results or Findings: PET/MRI provided ACC=98.75%, SN=98.75%, and PPV=100% for primary tumor detection, and ACC = 92.31%, SN = 84.62%, SP = 93.85%, PPV = 73.33%, NPV = 96.83% for LN detection. PET/MR parameters were able to predict LVSI (AUC= 80.16%), deep MI, p53abn and MMRd (AUC>70%). Less accurate predictions were found for EC histotype (AUC=68.04%) and infiltration pattern (AUC=65.19%). Finally, quantitative parameters could also predict both disease relapse (AUC=81.63%), with MTV and Size_CC showing the highest prognostic value, and the need to administer post-operative adjuvant therapy (AUC=74.63%).
Conclusion: [18F]FDG PET/MRI show good accuracy in the staging of EC primary tumor and LN metastases. Moreover, PET and MRI-derived parameters have a potential role in the characterization tumor aggressiveness and molecular alterations, as well as tumor recurrence prediction, crucial information for an optimal patient treatment and management in clinical practice.
Limitations: Molecular characterization not available for all patients.
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study received approval from the Institution’s Ethics Committee (protocol number 85/INT/2019) and informed consent was obtained from all patients in accordance with EC guidelines . All procedures were carried out in accordance with the Declaration of Helsinki (1964) and its later amendments.

Author Block: A. Milosevic¹, M. Chodyla¹, H. Steinberg¹, L. Kessler¹, B. M. Schaarschmidt¹, L. Umutlu¹, J. Grueneisen²; ¹Essen/DE, ²Munich/DE
Purpose: To asses the feasability of Diffusion Weighted Imaging (DWI) in staging of lymphoma patients to establish a radiation-free alternative to FDG-PET.
Methods or Background: A total of 181 lymphoma patients (mean age: 30.9 ± 19.1 years. 75 female and 106 male) undergoing clinically indicated 18F-FDG PET/MR examinations were retrospectivly assessed. 745 target lesions were assessed regarding Tracer-uptake (Standardized Uptake Values, SUV), diffusion restriction (Apparent Diffusion Coefficient, ADC), size and localization. Each of the target lesions was assigned a Deauville score. SUVs and ADC values were then compared using Spearman's rank correlation test. ROC-analysis was employed in order to find appropriate thresholds to distinguish between vital (score 4-5) and non-vital (score 1-3) manifestations in ADC-measurements,
Results or Findings: Calculated mean values for the ADCmin and ADCmean of targets with a Deauville score of 4 and 5 were significantly lower when compared to those lesions with a score of 1-3. Accordingly, ADCmean displayed a strong inverse correlation with the SUVs (r = -0.83). Furthermore, ROC analysis displayed an AUC of 0.91, 0.98 and 0,87 with a sensitivity of 87%, 93%, and 80% for ADCmin, ADCmean and ADCmax, respectively.
Conclusion: We highly recommend considering DWI an adjunct parameter for staging and restaging of lymphoma patients. DWI can be particularly helpful for individuals suffering from subtypes with low avidity to FDG and patient groups susceptible to radiation.
Limitations: Lack of proper gold standard for reference tissue in ADC meassurements. Thus, threshold levels were calculated manually.
Funding for this study: No funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: committee of university of Duisburg-Essen

Author Block: P. S. Choudhury, S. Chowdhury, M. Gupta, R. Kumar; Delhi/IN
Purpose: Oestrogen receptor (ER) is highly expressed in 70-80% of breast malignancies (BC). ER expression or absence plays a central role in its oncogenesis and is a prognostic and predictive biomarker. Molecular imaging with 18-F Fluroestradiol (FES) PET-CT targets ER and may have higher incremental value in guiding management by increasing specificity.
Methods or Background: We enrolled 57 female and 1 male breast cancer patient during initial staging and restaging as a part of an ongoing prospective study and performed 18-F FDG and 18-F FES within 1 week. Whole body FDG and FES PET-CT scan done from base of skull to mid thigh. Image of the breasts performed in prone position by hanging technique. The study was approved by scientific committee (Res/SCM/53/2022/67) and IRB (RGCIRC/IRB-BHR/112/2022). Lesion detection sensitivity was compared for a total number of lesions by McNemar test. FES was taken as reference in indeterminate lesions. Incremental value was reported by identifying FES exclusive lesions. Spearman rank test was used to co-relate ER expression and SUV max.
Results or Findings: FDG was more sensitive in lesion detection (80.3% vs 61.2% p<0.001) However FES detected more lesions in lobular variety (81.5% vs 56.2% p0.09). Significant co-relation seen between ER+ve and FES uptake. Significant incremental value of FES seen in 27% of patients with indeterminate lesions characterised by FES. Overall change in management noted in 21.1% (5.2% surgical and intent of management 15.8%).
Conclusion: Potential clinical applications of FES PET CT could be to select appropriate patients for hormonal therapies, resolving ER status of lesions non-invasively, solving clinical dilemmas when results of other investigations are inconclusive, systemic staging of breast cancers with low metabolic activity and selecting optimal doses for current or novel ER targeted therapies.
Limitations: Work in progress
Funding for this study: Radiopharmaceuticals were procured by the institution and the equipments used belongs to the institution. No other source of funding was used
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethics Committee letter reference : IRB (RGCIRC/IRB-BHR/112/2022)

Author Block: N. Sushentsev¹, G. Hamm¹, R. Manavaki¹, D. Soloviev², D. Lewis², L. Aloj¹, R. Goodwin¹, F. A. Gallagher¹, T. Barrett¹; ¹Cambridge/UK, ²Glasgow/UK
Purpose: We aimed at identifying a clinical metabolic imaging technique to differentiate Gleason score 7 (GS7) prostate tumours with dominant cribriform and non-cribriform Gleason pattern 4 (GP4) based on their comparative metabolic pathway enrichment analysis (MPEA).
Methods or Background: 28 prostate cancer (PCa) patients with n=39 GS7 lesions on prostatectomy were recruited, of which n=27 and n=12 harboured non-cribriform and cribriform GP4, respectively. The patients were divided into three sub-cohorts (A, B, and C), each encompassing n=13 GS7 lesions (n=9 non-cribriform; n=4 cribriform). In cohort A, n=39 fresh-frozen tumour samples were used for spatial metabolomics imaging to enable comparative MPEA between cribriform and non-cribriform GP4 epithelium. In cohort B, formalin-fixed-paraffin-embedded samples were immunohistochemically stained for fatty acid synthase (FASN) to corroborate the findings from cohort A. In cohort C, we determined standardised uptake value (SUVbw) for [1-11C]-acetate PET/CT in cribriform and non-cribriform GS7 lesions as a marker of fatty acid synthesis.
Results or Findings: In cohort A, MPEA highlighted fatty acid biosynthesis as the most significantly enriched pathway in cribriform GP4 epithelium compared to non-cribriform glands (fold change 4.2; Padj<0.0001). In cohort B, this aligned with a significantly increased expression of FASN in cribriform GS7 lesions compared to non-cribriform tumours (P=0.001). In cohort C, this corresponded to a significant increase in mean SUVbw of cribriform lesions compared to non-cribriform tumours (P<0.05 for all timepoints up to 60min post-injection). Conversely, the comparison of tumour-to-urine 1H-MRI ADCratio derived from the whole cohort showed no difference between the two GS7 phenotypes (P=0.56).
Conclusion: Clinical imaging of lipid metabolism is a biologically informed way of characterising cribriform and non-cribriform GS7 PCa, which is a challenge for 1H-MRI.
Limitations: Modest sample size dictated by study complexity.
Funding for this study: Prostate Cancer UK, Cancer Research UK, AstraZeneca
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: National Research Ethics Service Committee East of England, Cambridge South, Research Ethics Committee; study numbers: 16/EE/0205, 03/018. Cambridge University Hospitals Local Ethics Committee (CUH/15/EE/0213), and the Administration of Radioactive Substances Advisory Committee (ARSAC, certificate reference RPC/83/400/33606).

Author Block: N. Alan Selcuk, G. Beydagi, K. Akcay, B. B. Oven, S. Celik, L. Kabasakal; Istanbul/TR
Purpose: The aim of this study is to assess the potential efficacy of [68Ga]Ga FAPi PET/CT in staging and restaging in breast cancer patients with FDG-negative or low FDG uptake lesions.
Methods or Background: Between October 2020 and February 2024, 25 female patients with breast cancer were prospectively enrolled. These patients underwent [68Ga]Ga-FAPi and [18F]-FDG PET/CT imaging within one week for staging or restaging. The maximum standard uptake values (SUVmax) of the primary tumor areas and metastases in the [68Ga]Ga-FAPi and [18F]-FDG PET/CT images were recorded and statistically compared using the paired t-test.
Results or Findings: 25 female patients with suspicious primary malignancy recurrence or metastases but low FDG affinity were imaged with [68Ga]Ga-FAPi PET/CT. The mean age was 57.1±11.7 years. Histopathologic examination available for 20 patients revealed lobular carcinoma in 10 cases, ductal carcinoma in 8 cases, signet ring cell carcinoma in one patient and squamous cell carcinoma in one patient. In six patients (24%), neither the [18F]-FDG nor the [68Ga]Ga-FAPi PET/CT revealed any findings indicating recurrence or metastasis. Disease stage increased in 36% (n=9) of patients after [68Ga]Ga-FAPi PET/CT imaging, with 8 of them showing no pathologic findings on [18F]-FDG PET/CT. 60% (n=6) of the lobular carcinomas were upstaged after [68Ga]Ga-FAPi PET/CT. The detection of lymph nodes and distant metastases in lobular carcinoma was higher with [68Ga]Ga-FAPi PET/CT than with [18F]-FDG PET/CT. Furthermore, [68Ga]Ga-FAPi PET/CT showed a higher SUVmax in primary tumor foci and metastases (p<0.05).
Conclusion: [68Ga]Ga-FAPi PET/CT has been shown to be superior for staging in breast cancer, especially for lobular carcinoma with low FDG affinity. It is anticipated that [68Ga]Ga-FAPi PET/CT will be included in future guidelines for staging in breast cancer patients, especially in patients with lobular carcinoma.
Limitations: None
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethics committee approval no: 1576

Author Block: D. Kifjak, M. J. Hochmair, A. Korajac, S. Pochepnia, R-I. Milos, K. Sinn, A. Hoda, H. Prosch, L. Beer; Vienna/AT
Purpose: To evaluate the association between 18F-FDG-PET CT quantitative imaging markers of surgically resected mediastinal lymph nodes and histopathologic results in patients with operable non-small cell lung cancer (NSCLC) treated with neo-adjuvant combined immuno-chemotherapy.
Methods or Background: This preliminary analysis of a prospective, single-center study included 20 patients (8 male, 12 female) with NSCLC who were treated with neo-adjuvant combined immune-chemotherapy and underwent pre-operative 18F-FDG-PET-CT. We semi-automatically extracted the following parameters for each mediastinal lymph node station: metabolic tumor volume (MTV) and total lesion glycolysis (TLG) at pre-operative scans. The histological results of mediastinal lymph nodes were retrieved from patients’ records. A Mann-Whitney-U-Test was calculated to compare MTV/TLG and histological results for each mediastinal lymph node station.
Results or Findings: A total of 191 mediastinal lymph nodes were surgically removed. Four mediastinal lymph node metastases were found in three patients. In contrast 17 patients showed no tumor cells in their mediastinal lymph nodes. The median MTV for positive lymph nodes was 4.2 (range: 0-7.4) compared to 0 (range 0-4.3) for negative lymph nodes. The median TLG for positive lymph nodes was 6.3 (range 0-42) and for negative lymph nodes it was 0 (range 0-24). A statistically significant association between MTV and mediastinal lymph node metastases was observed, p=0.046. While there was a noticeable trend, no statistically significant association was identified between TLG and lymph node metastases, p=0.052.
Conclusion: High MTV values and to a lesser degree TLG are associated with residual lymph node metastases. However, both false positive (inflammation) and negative findings (micrometastatis) occur, thus limiting the ability of 18F-FDG-PET CT to predict histopathological response.
Limitations: Single-center study.
Selection bias, only patients with histologically confirmed lymph nodes were part of the study.
Funding for this study: The Austrian Federal Ministry for Digital and Economic Affairs, the National Foundation for Research, Technology and Development and the Christian Doppler Research Association is gratefully acknowledged.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Local IRB # 1521/2015

Author Block: F. Herr, C. A. Dascalescu, M. P. Fabritius, M. Brendel, C. Auernhammer, C. Spitzweg, J. Ricke, M. Heimer, C. C. Cyran; Munich/DE
Purpose: Integrated biomarkers of survival for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) receiving peptide receptor radionuclide therapy (PRRT) are still limited. This study aims to identify predictors of progression-free survival (PFS) in patients with GEP-NETs undergoing PRRT.
Methods or Background: This single-center retrospective study included 178 patients with GEP-NETs (G1 and G2) who received at least two consecutive cycles of PRRT with [177Lu]Lu-DOTA-TATE and underwent somatostatin receptor (SSTR) PET/CT before and after therapy. At baseline, an assessment was conducted in accordance with the Krenning score, and clinical parameters, including chromogranin A (CgA), neuron-specific enolase (NSE), hemoglobin, Ki-67, erythrocytes, C-reactive protein (CRP) and albumin were also collected. PFS was defined by a GEP-NET multidisciplinary team assessment.
Results or Findings: In univariate analysis at baseline, Krenning score 3, elevated levels of CgA (> 200 ng/dl) and NSE (>25 ng/dl) were significantly (p < 0.05) associated with shorter PFS. Ki-67 index > 5 %, primary tumor in the pancreas, levels of erythrocytes > 4 Mio/ µl, CRP > 1 mg/dl and albumin < 4.1 g/dl at baseline were also significantly (p<0.05) correlated with a shorter PFS. In multivariate analysis, Krenning score 3, CgA > 200 ng/ml, NSE > 35 ng/ml, and Ki-67 index > 5 % at baseline were significantly (p < 0.05) associated with shorter PFS. Including the Krenning score at baseline leads to a significant improvement of the cox regression model (p<0.05). Only the Ki-67 index (z=2.55) showed a higher z-score than the Krenning score at baseline (z = 2.41).
Conclusion: This study demonstrates the additional prognostic value of the Krenning score in conjunction with clinical parameters for patients with GEP-NET undergoing PRRT.
Limitations: Limitations of this study are its retrospective single-center design and the lack of multimodality imaging biomarkers.
Funding for this study: Wilhelm Vaillant Stiftung
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethics Committee of LMU-Munich – Project number: 20-1077

Author Block: T. R. Readford, P. Kench, M. Ugander, S. Patel, N. Giannotti; Sydney/AU
Purpose: Carotid atherosclerosis is a major contributor to the burden of cerebrovascular diseases. Conventional imaging is limited in interrogating the biological and functional characteristics that may increase plaque vulnerability. Multiple positron emission tomography/computed tomography (PET/CT) radiotracers provide novel diagnostic insights into plaque vulnerability and identify patients at higher risk of cerebrovascular events. This systematic review investigated the clinical role of PET radiotracers in identifying vulnerable carotid atherosclerotic plaque.
Methods or Background: A systematic review of the existing literature was performed using the following search strategy: ‘carotid’, ‘PET’, ‘atherosclerosis’, ‘plaque’ and ‘vulnerability’. Only original research articles were included. Covidence was used for data screening and data extraction.
Results or Findings: Thirty-nine studies were included that used 18F-fluorodeoxyglucose (18F-FDG), 18F-sodium fluoride (18F-NaF), 18F-fluoromisonidazole (18F-MISO), 68Ga-DOTATATE, 68Ga-Pentixafor and 11C-Acetate to target plaque metabolism-related inflammation, microcalcification, hypoxia, activated macrophages, C-X-C motif chemokine receptor4 and fatty acid synthesis, respectively. Seven studies used dual PET radiotracers with time intervals between scans ranging from one day to 4.8 months. Correlation between PET imaging and histology post-carotid endarterectomy was available in 17 studies. Authors noted agreement between macrophage-driven plaque inflammation by PET/CT and vulnerability-related morphological changes by MRI, suggesting complementary roles of combined MRI and PET/CT in detecting vulnerable plaque. Significant variability was observed in reported PET/CT acquisition techniques, injected radiotracer dose [18F-FDG: 185-925MBq, 18F-NaF: 125-370 MBq, 68Ga-DOTATATE: 148-157 MBq] and uptake times [18F-FDG: 50-180min ,18F-NaF: 60-180min, 68Ga-DOTATATE: 60-120min].
Conclusion: The use of multiple PET radiotracers may provide advanced diagnostic insights into carotid atherosclerotic plaque vulnerability. Further research is necessary to establish consensus on what constitutes a standard approach for the evaluation of vulnerable carotid plaque by PET/CT.
Limitations: Further quantitative analysis was limited by the variability of imaging parameters used across studies in this review.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: This was a systematic review of existing literature.

Author Block: C. Mingels¹, K. J. Chung¹, H. Nalbant¹, A. Willey¹, L. K. Shiyam Sundar², Y. G. Abdelhafez¹, R. Badawi¹, B. A. Spencer¹, L. Nardo¹; ¹Sacramento, CA/US, ²Vienna/AT
Purpose: Our aim was to identify the lower limit of injected dose for [18F]FDG Total-Body (TB) PET/CT in lymphoma therapy response assessment.
Methods or Background: In this prospective study 24 patients with biopsy-proven lymphoma were enrolled for interim or end-of-treatment TB PET/CT after 1h and 2h of the injection of ~3.0MBq/Kg [18F]FDG. Lower injected activities (1.0 MBq/kg, 0.5MBq/kg, 0.25MBq/kg, 0.125MBq/kg) were simulated. Lesions were segmented by an artificial intelligence-aided software and confirmed by an expert. Standardized-uptake values (SUVmax/mean/peak), metabolic tumor volume (MTV) and total-lesion glycolysis (TLG) were calculated. Additionally, total MTV (TMTV) was assessed for each patient. Liver and mediastinal blood-pool were used to calculate tumor-to-background ratio (TBR) and contrast-to-noise level (CNR). Therapy response assessment was performed by Deauville criteria.
Results or Findings: In total, 182 lymphoma lesions were analyzed. SUVmax/mean/peak, MTV, TLG, TBR and TMTV were not significantly different between reference standard and low-dose images. Image noise increased significantly with lower doses. CNR decreased significantly. Clinical therapy response assessment by Deauville Score was significantly lower between 0.125MBq/kg and reference standard (p<0.01) for 1h p.i. imaging. All other low-dose reconstructions revealed no significant differences. For 2h p.i. there was a significant difference in Deauville Score for 0.5MBq/kg, 0.25MBq/kg and 0.125MBq/kg compared to the reference standard (p<0.01). Deauville Scores for 1MBq/kg at 2h were not significantly different to the reference standard (p=0.16).
Conclusion: Dose reduction in therapy response assessment with TB PET/CT is possible to a lower limit of 0.25MBq/kg for 1h p.i. imaging and 1.0MBq/kg for 2h p.i. TB PET/CT. However, lower injected activities are at risk to underestimate the metabolic activity of the lymphoma lesions due to higher noise levels. TMTV and TLG were not different in ultra-low-dose [18F]FDG TB PET/CT.
Limitations: Small cohort, simulated low dose images
Funding for this study: The work was also supported by the In Vivo Translational Imaging Shared Resources with funds from NCI P30CA093373 and by the Fred and Julia Rusch Foundation for Nuclear Medicine Research and Education. Hande Nalbant’s funding is partially provided by United Imaging Health’s UIH Fellowship Gift.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the UC Davis institutional review board (IRB1470016). Written informed consent for inclusion was obtained. The study was performed in accordance with the Declaration of Helsinki.