CLR1404 / Cellectar - LARVOL DELTA

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry. (PubMed, Cancer Biother Radiopharm) - "Introduction: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. Therapeutic iopofosine I-131 studies demonstrated a variable, but linear relationship between iopofosine I-131 radiation dose and tumor growth delay (p < 0.05). Iopofosine I-131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing with CLR 124 presents a promising new treatment approach for personalizing administration of iopofosine I-131."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with I-CLR1404. (PubMed, Pharmaceutics) - "In addition, we have investigated how simple fits (exponential and biexponential) differ from the complete model. Such fits, despite providing a less accurate description of time-activity curves, may be a viable alternative when limited data is available in a practical case."

Journal • PK/PD data

Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer murine xenograft models (AACR 2018) - "CLR1404 is a radiolabeled alkylphophocholine analog with theranostic potential as a PET imaging agent (CLR 124, labeled with 124I) and as a radiotherapy agent (CLR 131, labeled with 131I). In this study, we demonstrated uptake of CLR 131 across multiple HNC cell lines and xenograft models with enhanced antitumor effects when CLR 131 is combined with XRT. These results suggest the potential value of TRT via CLR 131 combined with reduced dose XRT in HNC patients, which will be further tested in a phase I clinical trial."

Preclinical • Head and Neck Cancer

A kinetic model of continuous radiation damage to populations of cells: comparison to the LQ model and application to molecular radiotherapy. (PubMed, Phys Med Biol) - "We have also investigated the operation of the model in the continuous dose rate scenario, firstly by fitting pre-clinical data of tumor response to 131I-CLR1404 therapy, and secondly by showing how damage repair and proliferation rates can cause a treatment to achieve control or not. Kinetic models like the one presented in this work may be of special interest when modeling response to molecular radiotherapy."

Clinical • Journal • Oncology

Analysis of Cancer-targeting Alkylphosphocholine Analog Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood-Brain Barrier Model. (PubMed) - "Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). Moreover, addition of fluorescent moieties to APCs resulted in greater BMEC efflux via MRP and BCRP, and may affect fluorescence-guided applications. Overall, the characterization of APC analog permeability across human BBB is significant for advancing future brain tumor-targeted applications of these agents."

Journal • Biosimilar • Oncology • Solid Tumor

Targeted molecular radiotherapy of pediatric solid tumors using a radioiodinated alkyl-phospholipid ether analog. (PubMed, J Nucl Med) - "(131)I-CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with broad applicability in pediatric oncology. Since (131)I-CLR1404 has entered clinical trials in adults, our data warrants the development of pediatric clinical trials for this particularly vulnerable patient population."

Journal • Biosimilar • Oncology • Solid Tumor

Towards Integrated Treatment Planning of Combined External Beam Radiotherapy and Targeted Radionuclide Therapy (AAPM 2017) - " CLR1404, a small molecule, phospholipid ether analog exhibits selective sequestration in multiple solid tumors. This work demonstrates that personalized TRT treatment planning can be used in conjunction with EBRT to tailor specific doses to target tissues, maintain standard TPOs, and quantify the stimulating boost to systemic metastatic sites."

Clinical • Biosimilar • Oncology • Ophthalmology • Solid Tumor

Preclinical pharmacokinetics and dosimetry studies of [I/I]-CLR1404 for treatment of pediatric solid tumors in murine xenograft models. (PubMed, J Nucl Med) - "In this study, we evaluated the in vivo pharmacokinetics of I-CLR1404 (CLR 124) and estimated theranostic dosimetry for I-CLR1404 (CLR 131) MRT in murine xenograft models of the pediatric solid tumors neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma. CLR1404 is a suitable theranostic scaffold for dosimetry and therapy with potentially broad applicability in pediatric oncology. Given the ongoing clinical trials for CLR 131 in adults, this data supports the development of pediatric clinical trials and provides detailed dosimetry that may lead to improved MRT treatment planning."

Journal • PK/PD data • Oncology • Pediatrics • Sarcoma • Solid Tumor