TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Bundschuh, Ralph A.
A1  - Higuchi, Takahiro
A1  - Javadi, Mehrbod S.
A1  - Rowe, Steven P.
A1  - Zsótér, Norbert
A1  - Kroiss, Matthias
A1  - Fassnacht, Martin
A1  - Buck, Andreas K.
A1  - Kreissl, Michael C.
A1  - Lapa, Constantin
T1  - Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib
JF  - Endocrine
N2  - Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. 
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. 
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). 
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
KW  - personalized medicine
KW  - Positronen-Emissions-Tomografie
KW  - medullary thyroid carcinoma
KW  - tyrosine kinase inhibitor
KW  - TKI
KW  - vandetanib
KW  - 18F-FDG
KW  - positron emission tomography
KW  - 2-deoxy-2-(18F)fluoro-D-glucose
KW  - PET
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167910
SN  - 1355-008X
ER  - 
TY  - JOUR
A1  - Serfling, Sebastian E.
A1  - Lapa, Constantin
A1  - Dreher, Niklas
A1  - Hartrampf, Philipp E.
A1  - Rowe, Steven P.
A1  - Higuchi, Takahiro
A1  - Schirbel, Andreas
A1  - Weich, Alexander
A1  - Hahner, Stefanie
A1  - Fassnacht, Martin
A1  - Buck, Andreas K.
A1  - Werner, Rudolf A.
T1  - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
JF  - Molecular Imaging and Biology
N2  - Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.

Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.

Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.

Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
KW  - CXCR4
KW  - C-X-C motif chemokine receptor 4
KW  - PET
KW  - [68Ga]PentixaFor
KW  - [177Lu]/[90Y]PentixaTher
KW  - theranostics
KW  - endoradiotherapy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622
VL  - 24
IS  - 4
ER  -