Separation of radium and actinium from historical Th-229 sources for production of radioisotopes for targeted alpha immunotherapy

status: publishe

213Bismuth-labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

status: publishe

Bismuth-213 labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

status: publishe

The Therapeutic Potential of Anti-HER2 2Rs15d Nanobody Labeled with 225Ac – an In Vitro and In Vivo Evaluation

Human Epidermal Growth Factor Receptor type 2 (HER2) is overexpressed in numerous carcinomas and is often associated with a higher recurrence rate and a shorter time to relapse. Nanobodies (Nbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and targeted radionuclide therapy (TRT). HER2-targeting nanobodies are very attractive vectors for TRT, especially when labeled with α-particle emitters, which provide highly lethal and localized radiation to targeted cells with minimal exposure to surrounding healthy tissues. The aim of this study was to evaluate the therapeutic potential of the anti-HER2 Nb 2Rs15d labeled with 225Ac.JRC.G.I.5-Advanced Nuclear Knowledg

Combining Bismuth-213 with Nanobodies: finding the perfect match for Targeted Alpha Therapy

This study investigates a novel targeted therapy which combines the α-emitter Bismuth-213 (213Bi) and HER2-targeting nanobodies (Nbs) to selectively kill HER2+ metastases in breast- and ovarian cancer. The use of nanobodies as vehicles in TAT is promising due to their excellent in vivo properties, high affinity and specificity, fast diffusion and clearance kinetics. Moreover, Nbs show good tumor penetration due to their small size. The aim of this study is to develop and evaluate the in vitro binding characteristics on HER+ SKOV-3 cells, the in vitro stability using radio-ITLC and HPLC and the in vivo biodistribution of 213Bi-DTPA HER2 targeting Nb.JRC.G.I.5-Advanced Nuclear Knowledg

Preclinical Targeted α- and β−-Radionuclide Therapy in HER2-Positive Brain Metastasis Using Camelid Single-Domain Antibodies

HER2-targeted therapies have drastically improved the outcome for breast cancer patients. However, when metastasis to the brain is involved, current strategies fail to hold up to the same promise. Camelid single-domain antibody-fragments (sdAbs) have been demonstrated to possess favorable properties for detecting and treating cancerous lesions in vivo using different radiolabeling methods. Here we evaluate the anti-HER2 sdAb 2Rs15d, coupled to diagnostic γ- and therapeutic α- and β−-emitting radionuclides for the detection and treatment of HER2pos brain lesions in a preclinical setting. 2Rs15d was radiolabeled with 111In, 225Ac and 131I using DTPA- and DOTA-based bifunctional chelators and Sn-precursor of SGMIB respectively and evaluated in orthotopic tumor-bearing athymic nude mice. Therapeutic efficacy as well as systemic toxicity were determined for 131I- and 225Ac-labeled sdAbs and compared to anti-HER2 monoclonal antibody (mAb) trastuzumab in two different HER2pos tumor models. Radiolabeled 2Rs15d showed high and specific tumor uptake in both HER2pos SK-OV-3-Luc-IP1 and HER2pos MDA-MB-231Br brain lesions, whereas radiolabeled trastuzumab was unable to accumulate in intracranial SK-OV-3-Luc-IP1 tumors. Administration of [131I]-2Rs15d and [225Ac]-2Rs15d alone and in combination with trastuzumab showed a significant increase in median survival in 2 tumor models that remained largely unresponsive to trastuzumab treatment alone. Histopathological analysis revealed no significant early toxicity. Radiolabeled sdAbs prove to be promising vehicles for molecular imaging and targeted radionuclide therapy of metastatic lesions in the brain. These data demonstrate the potential of radiolabeled sdAbs as a valuable add-on treatment option for patients with difficult-to-treat HER2pos metastatic cancer.JRC.G.I.5-Advanced Nuclear Knowledg