TY  - JOUR
A1  - Boschert, Verena
A1  - Teusch, Jonas
A1  - Müller-Richter, Urs D. A.
A1  - Brands, Roman C.
A1  - Hartmann, Stefan
T1  - PKM2 modulation in head and neck squamous cell carcinoma
JF  - International Journal of Molecular Sciences
N2  - The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.
KW  - HNSCC
KW  - head and neck cancer
KW  - cancer metabolism
KW  - glycolysis
KW  - PKM2
KW  - Warburg effect
KW  - CD44
KW  - Compound 3k
KW  - DASA-58
KW  - AMPK
KW  - TXNIP
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284458
SN  - 1422-0067
VL  - 23
IS  - 2
ER  - 
TY  - JOUR
A1  - Linz, Christian
A1  - Brands, Roman C.
A1  - Kertels, Olivia
A1  - Dierks, Alexander
A1  - Brumberg, Joachim
A1  - Gerhard-Hartmann, Elena
A1  - Hartmann, Stefan
A1  - Schirbel, Andreas
A1  - Serfling, Sebastian
A1  - Zhi, Yingjun
A1  - Buck, Andreas K.
A1  - Kübler, Alexander
A1  - Hohm, Julian
A1  - Lapa, Constantin
A1  - Kircher, Malte
T1  - Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity – initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.

Methods
Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference.

Results
[\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples.

Conclusion
FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.
KW  - molecular imaging
KW  - fibroblast activation protein
KW  - head and neck cancer
KW  - PET
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307246
SN  - 1619-7070
SN  - 1619-7089
VL  - 48
IS  - 12
ER  -