Anti-Tumour Agents

Ref: 10628
A Novel Class of Compounds for BNCT of Tumours and for PET imaging, with Potential for Increased Selectivity Towards Tumour Cells and for Tumours in the CNS.

Key advantages
  • A novel class of carborane-containing arylphosphonium salts with potential as tumour-selective BNCT or PET agents
  • Selective uptake into cancer cells
  • Good in vitro cytotoxicity

The invention

Image from Dalton Transactions, 2007, 1982

Image from Dalton Transactions, 2007, 1982

Delocalised lipophilic cations (DLCs) are ideal for application as tumour imaging and anti-cancer agents due to their physical properties, lipophilicity and delocalized positive charge.

They can readily traverse the lipophilic mitochondrial membrane and accumulate in the mitochondria. Furthermore, the significant increase in negative electrical potential across the mitochondrial membrane of cancer cells compared to healthy cells results in preferential accumulation of the charged DLCs in tumour cells. Phosphonium salts show particular promise, for example triphenylmethylphosphonium (TPMP) salts have demonstrated highly cancer-selective accumulation and cyctotoxicity.

Radio-labelled TPMP iodide has been studied as a PET imaging agent for canine brain tumours. The compound was rapidly taken up and retained in the tumour 48 fold higher than healthy tissue (an order of magnitude higher than other available glioma PET tracers or boron neutron capture therapy (BNCT) agents).

This high uptake and retention in CNS tumours is particularly significant due to the resistance of many of these tumours to current therapies. Boron-containing analogues of TPMP can potentially facilitate selective delivery of boron to tumours, suitable for BNCT.

Once accumulated selectively in the tumour cells, the boron nuclei can capture slow, “thermal” neutrons from a neutron beam and emit a-particles and 7Li ions. They are therefore proposed as an ideal method for selectively delivering high-LET radiation to tumour cells.

Novel arylphosphonium salts containing a closo-carborane have been synthesised. These are the first examples of such compounds, representing a new class of compounds with potential as BNCT or PET agents.

Preliminary in vitro cytotoxicity against the SF268 (human glioblastoma) cell line demonstrated toxicity below the assay limits (GI¬50>40µM) and at least 4-fold lower than the control, TPMP. This is extremely promising and further tests are in progress.

Carborane derivatives and zwitterionic species are currently being evaluated in detail for tumour cell uptake and biodistribution. Synthetic chemistry and lead optimisation is ongoing. The synthetic route provides substantial scope for compound optimisation.


Agents for BNCT of tumours or PET imaging of tumours, particularly in the CNS.

Principal inventors

  • Dr. Louis Rendina

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