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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
Scientific reports, 06/2020, Letnik: 10, Številka: 1Journal Article
Abstract The clinical translation of theranostic 177 Lu-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 177 Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177 Lu-scFvD2B was obtained in high yield and stability. In vitro , 177 Lu-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 177 Lu-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 177 Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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