Journal Article DKFZ-2023-01153

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Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5.

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2023
Molecular Diversity Preservation International Basel

International journal of molecular sciences 24(11), 9420 () [10.3390/ijms24119420]
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Abstract: Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide 177Lu. The resulting radiolabeled mAb ([177Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [177Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [177Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Male (MeSH) ; Pentetic Acid: chemistry (MeSH) ; Tissue Distribution (MeSH) ; Prostate (MeSH) ; Cell Line, Tumor (MeSH) ; Antibodies, Monoclonal: therapeutic use (MeSH) ; Antibodies, Monoclonal: chemistry (MeSH) ; Stem Cells (MeSH) ; Carcinoma: drug therapy (MeSH) ; Lutetium: chemistry (MeSH) ; 177Lu-labeled antibody ; CHX-A″-DTPA ; prostate cancer ; prostate stem cell antigen ; Pentetic Acid ; Antibodies, Monoclonal ; Lutetium

Classification:

Contributing Institute(s):
  1. DKTK DD zentral (DD01)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023
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Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2023-06-12, last modified 2024-02-29


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