Tackling these issues, researchers in Canada are developing an implantable depot from which gold nanoparticles diffuse gradually and reproducibly into the tumour over several days. Measuring 4 x 0.8 mm, the same size as a standard brachytherapy seed, the gelatinous calcium alginate cylinders are implantable using clinical brachytherapy needles. The approach is a potential alternative for localized tumours currently treated with seed brachytherapy, such as prostate and breast cancer.

The University of Toronto researchers used the depots to reduce undesirable dose hotspots, which are common in seed brachytherapy, up to three-fold in their latest study. The research also revealed depots containing the long-range beta emitter yttrium-90 delivered the most homogeneous dose distribution of three radioisotopes tested (Phys. Med. Biol. 62 8581).

Dose simulations

First author Priscilla Lai and co-authors made the findings using MCNP5 Monte Carlo simulations of depots containing 15 nm gold nanoparticles tagged with yttrium-90, lutetium-177 and indium-111. The radioisotopes emit electrons with a range of energies and corresponding short (0.6 mm), mid (1.7 mm) and long (11 mm) ranges in tissue. Easy to shield, electron emitters are convenient to use in radiation safety terms, but also offer important dosimetric advantages for the highly localized nanoparticle-guided treatments.

"The dose distributions from electron emitters are much more conformal than photon-based radiation since they only travel a finite range in tissues before they are entirely absorbed," explained Lai. "This would be advantageous for treatment of diseased tissues which are very close to critical structures, such as the chest wall for breast cancer or the urethra for prostate cancer."

The researchers simulated a single depot and four depots arranged 4.5 mm apart in a square, as well as identical arrangements of brachytherapy seeds, which deliver dose through low-energy photons. They selected the activities of each radioisotope to deliver approximately the same integrated dose.

The simulations demonstrated that the depots produced significantly lower dose hotspots than the seeds, as the diffusion of the nanoparticles "smoothed" the maxima. In the square arrangement, for example, the maximum dose was 2.8, 3.4 and 2.7 times lower in simulations with yttrium-90, lutetium-177 and indium-111, respectively.

Greater dose coverage and homogeneity in the simulated volumes were observed for yttrium-90, the longer-range electron emitter, compared with the other two radioisotopes. For example, in the yttrium-90 simulation, all of the simulated volume received dose. In simulations of lutetium-177 and indium-111, however, some of the volumes received no dose.

The team observed similar effects in a separate experiment where mouse models with human breast cancer xenografts were implanted with single depots, in a comparison with tumours directly injected with nanoparticles. The resulting radioisotope distributions were imaged using SPECT and used to predict dose rates and calculate integrated dose distributions.

There is still scope to improve dose homogeneity, however, as previous work by the researchers demonstrated that large nanoparticles mostly remain in the depots. Smaller nanoparticles than those in the current study could be used to increase diffusion and dose homogeneity, the researchers concluded.

Based on their findings to date, the researchers are optimistic that cancer patients will benefit from the nanoparticle depots following further pre-clinical research and clinical trials. Applications of the depots could also extend beyond radiotherapy.

"We are excited about this new treatment approach because it creates new opportunities for not only delivering radiolabelled nanoparticles, but many other forms of nanomedicine," senior author Raymond Reilly told medicalphysicsweb. "Nanoparticles that incorporate other therapeutic agents for cancer such as chemotherapy could potentially be delivered locally to tumours using the depots."