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Purpose: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer., Methods: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [ 68 Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [ 68 Ga]Ga-FAPI-46 PET/CT results., Results: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [ 68 Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUV max 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUV max 17.9 (16.4 - 23.5) on [ 68 Ga]Ga-FAPI-46 PET/CT., Conclusion: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [ 68 Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: [ 68  Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [ 68  Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging., Materials and Methods: Eighteen patients underwent [ 68  Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard., Results: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [ 68  Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [ 68  Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging., Conclusion: In summary, this innovative [ 68  Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning., (© 2024. The Author(s).)

Background: [ 68 Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [ 18 F]FDG in UC, [ 68 Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [ 68 Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors., Methods: Fifteen patients with UC prior to or after local treatment underwent [ 68 Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUV mean and SUV max ). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT)., Results: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUV max 20.8 (range, 8.1-27.8)) followed by lymph node metastases (SUV max 10.6 (range, 4.7-29.1)). In 4/15 (26.7%) patients there were [ 68 Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy., Conclusion: [ 68 Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [ 68 Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients., (© 2022. The Author(s).)

Background: 68 Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68 Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC., Methods: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68 Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUV mean ) and SUV max measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually., Results: Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUV max of 4.35 and SUV mean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUV max 9.05 (4.86-29.16)), followed by bone metastases (SUV max 5.56 (0.97-15.85)), and lymph node metastases (SUV max 3.90 (2.13-6.28)) and visceral metastases (SUV max 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68 Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines., Conclusion: Targeting c-MET expression, 68 Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68 Ga-EMP-100 as a biomarker in mRCC patients., (© 2021. The Author(s).)

Purpose: To investigate differences in standard preoperative inflammatory markers in patients with urothelial carcinoma (UC) and variant histologies undergoing radical cystectomy (RC) and determine its impact on survival., Methods: Patients undergoing RC at an academic high-volume center were retrospectively analyzed. Preoperatively taken CRP, leukocytes, hemoglobin (Hb), and thrombocytes were analyzed as routine inflammatory biomarkers. Log-rank tests and Kruskal-Wallis analysis were used to calculate for differences in survival and in blood levels of biomarkers., Results: 886 patients with complete follow-up and UC or variant histology underwent RC at our institution between 2004 and 2019. Although variant histology presents with significantly higher t stage than UC, cancer-specific survival (CSS) of UC (1-year-CSS: 93%) is not significantly different to variant histology of UC with squamous differentiation (UCSD, 1-year-CSS: 81%), squamous cell carcinoma (SCC, 1-year-CSS: 82%), and adenocarcinoma (AC, 1-year-CSS: 81%). In UC, alterations in all biomarkers except leukocytes beyond routine cut-off values were associated with poor survival (p < 0.01), whereas Hb beyond cut-off values are associated with poor prognosis in SCC (p < 0.05). CRP levels are significantly elevated in UCSD and SCC at time of surgery compared to UC (p < 0.05)., Conclusion: Inflammatory biomarkers reveal distinctive patterns across UC and variant histologies of bladder cancer. As inflammation might play an important role in cancer progression, further research is warranted to understand those molecular mechanisms and their potential therapeutic impact in variant histology of bladder cancer., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Delineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68 Ga-labeled ligands; nonetheless, 18 F-labeled PET ligands are gaining increasing importance due to advantages over 68 Ga-labeled compounds. However, standardized tumor delineation methods for 18 F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18 F-PSMA-1007 PET., Methods: Fifty patients with metastatic prostate cancer, 18 F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUV max (SUV%), and thresholds relative to III) liver (SUV liver ), IV) parotis (SUV parotis ) and V) spleen (SUV spleen )., Results: A fixed SUV of 4.0 (r=0.807, r 2 = 0.651, p<0.001) showed the best overall association with the volumetric reference. 55% SUV max (r=0.627, r 2 = 0.393, p<0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUV liver (r=0.715, r 2 = 0.511, p<0.001), 80% SUV parotis (r=0.762, r 2 = 0.581, p<0.001) and 60% SUV spleen (r=0.645, r 2 = 0.416, p<0.001). Background tissues SUV liver, SUV parotis & SUV spleen did not correlate (p>0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUV max , 42% SUV max and 20% SUV max ) revealed inferior association for LNM delineation., Conclusions: A threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mittlmeier, Brendel, Beyer, Albert, Todica, Zacherl, Wenter, Herlemann, Kretschmer, Ledderose, Schmidt-Hegemann, Kunz, Ricke, Bartenstein, Ilhan and Unterrainer.)

We present a 71-year-old female patient who underwent 18 F-PSMA-1007 PET/CT for suspected metastatic renal cell carcinoma (RCC), as RCC also shows high PSMA-expression in tumor neovascularization. 18 F-PSMA-1007 PET/CT showed a high PSMA-avidity in the renal tumor, enlarged intra-abdominal and mediastinal lymph nodes. Moreover, PSMA-positive pleural, pulmonal and osseous lesions were found. However, histopathology revealed an immature plasma cell myeloma with an endothelial PSMA-expression of the neovasculature. This case illustrates the increased PSMA-avidity in multiple myeloma and highlights PSMA as a potential theragnostic target in multiple myeloma. For clinical routine, lymphatic diseases such as extramedullary myeloma should be considered as differential diagnosis in PSMA-avid renal masses on PET/CT.