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  - 
TY  - JOUR
A1  - Buck, Andreas K.
A1  - Serfling, Sebastian E.
A1  - Lindner, Thomas
A1  - Hänscheid, Heribert
A1  - Schirbel, Andreas
A1  - Hahner, Stefanie
A1  - Fassnacht, Martin
A1  - Einsele, Hermann
A1  - Werner, Rudolf A.
T1  - CXCR4-targeted theranostics in oncology
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
KW  - CXCR4
KW  - theranostics
KW  - C-X-C motif chemokine receptor 4
KW  - [68Ga]PentixaFor
KW  - [177Lu]PentixaTher
KW  - [90Y]PentixaTher
KW  - endoradiotherapy
KW  - adrenocortical carcinoma
KW  - multiple myeloma
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324545
VL  - 49
IS  - 12
ER  -