PDC Delivery Platform

Targeted delivery of diverse oncologic payloads




Cellectar’s product candidates are built upon a cancer cell-targeting delivery and retention platform of optimized phospholipid ether drug conjugates (PDCs). Cellectar’s proprietary PLE carrier platform was deliberately designed to be coupled with multiple payloads to facilitate both therapeutic and diagnostic applications. Several payloads have been conjugated to provide/allow for the targeted delivery of radiotherapeutics, chemotherapeutics, and molecular diagnostics.


After systemic administration, our PDCs bind to lipid rafts in tumor cell membranes and enter the tumor cells in a clathrin-independent manner. Research has shown that Cellectar’s PDCs feature a number of unique attributes that make them a compelling and scalable oncology delivery platform:

  • Excellent safety and tolerability profile of the delivery vehicle, which has not shown any toxicities in clinical studies
  • Selective uptake and prolonged retention of PDCs by cancer cells and cancer stem cells
  • Broad-spectrum targeting of liquid and solid cancers
  • The capacity to deliver large payload molecules allows for a wide spectrum of therapeutic or diagnostic agents to be attached


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Selective uptake of a fluorescent PDC imaged in a range of cancer cell line and cancer stem cells

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Clinical translation into humans: To date, CLR 131 and CLR 124 have been administered to more than 100 patients and has been well tolerated. Clinical data support the selective uptake and prolonged retention see in vitro and in preclinical models.

Cellectar has based the development of our proprietary compounds on the key discovery that selective retention by malignant tumor cells depends on specific properties of the PLEs. These properties include the structure and length of the molecule’s ‘backbone’, the structure of the molecule’s head group, and the overall charge on the molecule. By performing extensive structure-activity relationship (SAR) studies in which multiple PLEs were synthesized and key molecular features that are critical for both increased malignant tumor uptake and selective retention were identified.

 Selective uptake and retention of PDCs in malignant cells and tumors

The basis for selective tumor targeting of our PDC compounds lies in differences between the plasma membranes of cancer cells as compared to those of most normal cells. Specifically, cancer cell membranes are highly enriched in lipid rafts. Lipid rafts are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids and serve to organize cell surface and intracellular signaling molecules. In vitro studies using fluorescent PDCs (CLR 1501 and CLR 1502) suggest that lipid rafts serve as portals of entry for PDCs. Furthermore, disruption of the lipid raft architecture significantly reduces the uptake of our PLEs into cancer cells. These experiments have also demonstrated the selective uptake and prolonged retention in cancer cells versus non-cancerous cells. This selectivity of our compounds for cancer cells is attributed to the high affinity of the PLE carrier for cholesterol and the abundance of cholesterol-rich lipid rafts in cancer cells as compared to non-cancer cells. Cellectar’s PDCs transported into the cytoplasm via clathrin-independent endocytosis.



Axial images and volume rendering of a CLR 124 PET/MR data set of brain metastases imaged in a lung cancer patient. The 3D volume rendering illustrated Gadolinium (MR contrast agent)-positive areas in yellow and areas of CLR 124 uptake in blue.

Cellectar Biosciences, Inc.

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About PDCs
Cellectar’s PDC Platform

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