Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody
نویسندگان
چکیده
Background: Osteosarcoma (OS) represents the most common primary bone tumor in humans and companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend survival of patients with OS. Here, we examine dosimetry beagle dogs cross-reactivity human tissues novel antibody, IF3, that targets insulin growth factor receptor type 2 (IGF2R), which overexpressed on OS cells, making it candidate radioimmunotherapy Methods: [89Zr]Zr-DFO-IF3 was injected into three healthy dogs. PET/CT conducted at 4, 24, 48, 72 h. RAPID analysis used determine [177Lu]Lu-CHXA”-IF3 clinical trial IF3 antibody biotinylated, multitude were assessed immunohistochemistry. Results: revealed only liver, marrow, adrenal glands had high uptake. Clearance initially through renal hepatobiliary excretion first h followed by primarily physical decay. showed marrow be dose-limiting organ therapeutic range 177Lu calculated 0.487–0.583 GBq. Immunohistochemistry demonstrated absence IGF2R expression surface thus suggesting will well tolerated. Conclusions: Image-based has defined safe canine trials, while immunohistochemistry suggested not cross-react tissues.
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ژورنال
عنوان ژورنال: Pharmaceuticals
سال: 2023
ISSN: ['1424-8247']
DOI: https://doi.org/10.3390/ph16070979