For those with scientific interest in Y90 delivery

I found this in a research paper on another topic, with implication that the resin-microspheres used by SRX (and by extension the glass microspheres used by BTG) could be improved.  I have no constructive comment to add other than passing this paper on!

http://www.thno.org/v06p0918.pdf

Selective Internal Radiation Therapy (SIRT)
SIRT is another clinically approved local delivery method for internal radiation therapy. This approach delivers radioactive microspheres loaded with 90Y to the liver via a surgically implanted catheter that is fed up the hepatic artery. It is known that while the portal vein provides the majority of the blood supply to healthy hepatocytes in the liver, liver tumors are fed by the hepatic artery. Thus, introduction of microspheres through the hepatic artery selectively target the tumor regions. Commercially available microsphere formulations such as Sir-Spheres by Sirtex are approximately 30μm in diameter, which prevent cellular uptake and deep tumor penetration, but also help retain the microspheres around the tumor site while minimizing clearance through the hepatic capillaries. SIRT is currently in several phase II and III clinical trials for use in combination with front-line chemotherapeutics against hepatocellular carcinoma (HCC) and advanced metastatic colorectal cancer65, 66. The data from recent clinical trials show that 90Y-SIRT + systemic chemotherapy provides significantly more hepatic progression-free survival than chemotherapy alone while maintaining tolerable liver and lung toxicity .

Although local hepatic delivery using 90Y-microspheres for SIRT has shown success, there are areas in which it can be improved. Most notably, the lack of tumor penetration by the microspheres requires a high-energy β emitter with a long depth of penetration to reach the deeper tumor tissue. To maximize the absorbed dose to deep tumor cells, a large dose must be provided at the tumor periphery, which increases toxicity to healthy liver tissue. A future 177Lu-LCP-SIRT therapy may be able to address these issues. With a diameter of just 40-60 nm, the much smaller 177Lu-LCP could penetrate much deeper into the tumor mass, and the addition of an appropriate targeting ligand would allow selective uptake of the particles into the tumor cells themselves, bringing the radioactive payload closer to the target DNA in the cell nucleus. The lower energy and shorter depth of penetration of 177Lu’s β emissions may then be adequate to treat the entire tumor at a lower total dose and with less toxicity to nearby healthy tissue, although the efficacy of 177Lu as the encapsulated radionuclide should be compared with 90Y. If 177Lu-LCP is effective, the γ decay from 177Lu could then allow simultaneous confirmation of 177Lu-LCP accumulation in the tumor mass via SPECT imaging. Additionally, 177Lu-LCP could be easily co-loaded with a phosphorylated chemotherapeutic for localized chemoradiation therapy.
The much smaller size of LCP compared to Sir-Spheres also presents new challenges regarding the clearance of 177Lu away from the tumor site, not only from those particles that are injected into the hepatic artery and do not enter the tumor mass, but also from any radiation that initially enters the tumor and exits at a later time. To ensure maximal tumor accumulation and minimal clearance of 177Lu-LCP through the vena cava, simple changes to the surface of the particle should be made to encourage interaction with the tumor cell membrane and increase receptor-mediated endocytosis, such as modifying the outer leaflet with cationic lipids, lowering the surface PEG density, and adding a high affinity targeting ligand. Peptide targeting ligands may be the most successful class of ligand for this purpose, as they generally bind with higher affinity than small molecule ligands, and are less bulky, expensive, and immunostimulatory than antibodies. Peptide ligands against the α6β1 receptor overexpressed in human colon cancer cells may be successful against liver metastasis67, 68, and similarly, overexpression of glypican-3 (GPC-3) in HCC has allowed synthesis and use of targeted peptides69, 70. Changes in the nanoparticle injection speed should also be considered, as a slower infusion of particles into the tumor will avoid saturation of the surrounding blood vessels and tumor cell receptors. The introduction of novel nanodelivery approaches does indeed present new challenges in local delivery of radioisotopes, but the advantages posed by these new methods should make overcoming these challenges a worthwhile venture.