TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Higuchi, Takahiro
A1  - Pomper, Martin G.
A1  - Rowe, Steven P.
T1  - Theranostics in oncology — thriving, now more than ever
JF  - Diagnostics
N2  - Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue Novel Theranostic Agents, nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever.
KW  - theranostics
KW  - somatostatin receptor (SSTR)
KW  - prostate-specific membrane antigen (PSMA)
KW  - prostate cancer
KW  - neuroendocrine neoplasms (NEN)
KW  - neuroendocrine tumors (NET)
KW  - meningioma
KW  - norepinephrine transporter
KW  - neuroblastoma
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236662
SN  - 2075-4418
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Chen, Xinyu
A1  - Werner, Rudolf A.
A1  - Koshino, Kazuhiro
A1  - Nose, Naoko
A1  - Mühlig, Saskia
A1  - Rowe, Steven P.
A1  - Pomper, Martin G.
A1  - Lapa, Constantin
A1  - Decker, Michael
A1  - Higuchi, Takahiro
T1  - Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
JF  - Theranostics
N2  - Background: Radiolabeled agents that are substrates for the norepinephrine transporter (NET) can be used to quantify cardiac sympathetic nervous conditions and have been demonstrated to identify high-risk congestive heart failure (HF) patients prone to arrhythmic events. We aimed to fully characterize the kinetic profile of the novel \(^{18}\)F-labeled NET probe AF78 for PET imaging of the cardiac sympathetic nervous system (SNS) among various species.

Methods: \(^{18}\)F-AF78 was compared to norepinephrine (NE) and established SNS radiotracers by employing in vitro cell assays, followed by an in vivo PET imaging approach with healthy rats, rabbits and nonhuman primates (NHPs). Additionally, chase protocols were performed in NHPs with NET inhibitor desipramine (DMI) and the NE releasing stimulator tyramine (TYR) to investigate retention kinetics in cardiac SNS.

Results: Relative to other SNS radiotracers, 18F-AF78 showed higher transport affinity via NET in a cell-based competitive uptake assay (IC\(^{50}\) 0.42 ± 0.14 µM), almost identical to that of NE (IC\(^{50}\), 0.50 ± 0.16 µM, n.s.). In rabbits and NHPs, initial cardiac uptake was significantly reduced by NET inhibition. Furthermore, cardiac tracer retention was not affected by a DMI chase protocol but was markedly reduced by intermittent TYR chase, thereby suggesting that \(^{18}\)F-AF78 is stored and can be released via the synaptic vesicular turnover process. Computational modeling hypothesized the formation of a T-shaped π-π stacking at the binding site, suggesting a rationale for the high affinity of \(^{18}\)F-AF78.

Conclusion: \(^{18}\)F-AF78 demonstrated high in vitro NET affinity and advantageous in vivo radiotracer kinetics across various species, indicating that \(^{18}\)F-AF78 is an SNS imaging agent with strong potential to guide specific interventions in cardiovascular medicine.
KW  - norepinephrine transporter
KW  - T-shaped π-π stacking
KW  - nonhuman primates
KW  - radiotracer kinetics
KW  - cardiac innervation imaging
KW  - sympathetic nervous system
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300685
VL  - 12
IS  - 9
SP  - 4446
EP  - 4458
ER  -