“…5 . The figure, like the results summarized below unless otherwise specified, is taken from a recently published study on [ 177 Lu]PentixaTher biokinetics and dosimetry [ 46 ]. Fig.…”
“…However, it must be considered in myeloablative treatment that the long residence time of the activity in the bone marrow requires a long decay time before a stem cell transplantation can be safely performed. Therefore, in order to reduce the duration of the phase of aplasia and the associated risk of threatening complications, therapy is usually performed with the nuclide 90 Y instead of 177 Lu [ 46 ].…”
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 [177Lu]/[90Y]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.
“…5 . The figure, like the results summarized below unless otherwise specified, is taken from a recently published study on [ 177 Lu]PentixaTher biokinetics and dosimetry [ 46 ]. Fig.…”
“…However, it must be considered in myeloablative treatment that the long residence time of the activity in the bone marrow requires a long decay time before a stem cell transplantation can be safely performed. Therefore, in order to reduce the duration of the phase of aplasia and the associated risk of threatening complications, therapy is usually performed with the nuclide 90 Y instead of 177 Lu [ 46 ].…”
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 [177Lu]/[90Y]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.
“…Since CXCR4 is overexpressed on the surface of hematological cancer cells, 177 Lu-and 90 Y-labeled Pentixather have been evaluated as adjunct to high-dose chemotherapy in this cancer type. This resulted in a more beneficial outcome of the combination therapy vs monotherapy with the radioligand [183,184]. In addition, a case study in B-cell lymphoma patients demonstrated the possibility of a theranostic approach with [ 68 Ga]Ga-Pentixafor and [ 177 Lu]Lu-Pentixather [185].…”
Targeted radionuclide theranostics is becoming more and more prominent in clinical oncology. Currently, most nuclear medicine compounds researched for cancer theranostics are directed towards targets expressed in only a small subset of cancer types, limiting clinical applicability. The identification of cancer-specific targets that are (more) universally expressed will allow more cancer patients to benefit from these personalized nuclear medicine–based interventions. A tumor is not merely a collection of cancer cells, it also comprises supporting stromal cells embedded in an altered extracellular matrix (ECM), together forming the tumor microenvironment (TME). Since the TME is less genetically unstable than cancer cells, and TME phenotypes can be shared between cancer types, it offers targets that are more universally expressed. The TME is characterized by the presence of altered processes such as hypoxia, acidity, and increased metabolism. Next to the ECM, the TME consists of cancer-associated fibroblasts (CAFs), macrophages, endothelial cells forming the neo-vasculature, immune cells, and cancer-associated adipocytes (CAAs). Radioligands directed at the altered processes, the ECM, and the cellular components of the TME have been developed and evaluated in preclinical and clinical studies for targeted radionuclide imaging and/or therapy. In this review, we provide an overview of the TME targets and their corresponding radioligands. In addition, we discuss what developments are needed to further explore the TME as a target for radionuclide theranostics, with the hopes of stimulating the development of novel TME radioligands with multi-cancer, or in some cases even pan-cancer, application.
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