Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
| Autor: | Carpanese, Debora, Ferro-Flores, Guillermina, Ocampo-Garcia, Blanca, Santos-Cuevas, Clara, Salvarese, Nicola, Figini, Mariangela, Fracasso, Giulio, De Nardo, Laura, Bolzati, Cristina, Rosato, Antonio, Meléndez-Alafort, Laura |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glutamate Carboxypeptidase II
Male Immunoconjugates Single Photon Emission Computed Tomography Computed Tomography Science Immunoglobulin Variable Region Mice Nude Lutetium urologic and male genital diseases THERAPY Article Tumour biomarkers Heterocyclic Compounds 1-Ring Antineoplastic Agents Immunological Target identification Cell Line Tumor PSMA Animals Humans Tissue Distribution Precision Medicine FRAGMENT Radioisotopes Prostate Cancer single chain Prostatic Neoplasms CANCER Xenograft Model Antitumor Assays 177Lu-scFvD2B NUDE-MICE Preclinical research ANTIBODIES Antigens Surface PC-3 Cells Medicine LIGANDS Radiopharmaceuticals RENAL UPTAKE lutetium 177 Immunotheranostic Single-Chain Antibodies |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports Scientific reports (Nature Publishing Group) 10 (2020): 9313-1–9313-10. doi:10.1038/s41598-020-66285-2 info:cnr-pdr/source/autori:Carpanese D.; Ferro-Flores G.; Ocampo-Garcia B.; Santos-Cuevas C.; Salvarese N.; Figini M.; Fracasso G.; De Nardo L.; Bolzati C.; Rosato A.; Melendez-Alafort L./titolo:Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen/doi:10.1038%2Fs41598-020-66285-2/rivista:Scientific reports (Nature Publishing Group)/anno:2020/pagina_da:9313-1/pagina_a:9313-10/intervallo_pagine:9313-1–9313-10/volume:10 |
| DOI: | 10.1038/s41598-020-66285-2 |
| Popis: | The clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177Lu-scFvD2B was obtained in high yield and stability. In vitro, 177Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidneys. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy. |
| Databáze: | OpenAIRE |
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