Improved tumour response prediction with equivalent uniform dose in pre-clinical study using direct intratumoural infusion of liposome-encapsulated¹⁸⁶Re radionuclides

Abstract

Crucial to all cancer therapy modalities, is a strong correlation between treatment and effect. Predictability of therapy success/failure allows for the optimization of treatment protocol and aids in the decision of whether additional treatment is necessary to prevent tumour progression. This work evaluated the relationship between cancer treatment and effect for intratumoural infusions of liposome-encapsulated 186 Re to head and neck squamous cell carcinoma xenografts of nude rats. Absorbed dose calculations using a dose point kernel convolution technique showed significant intratumoural dose heterogeneity due to the short range of the beta-particle emissions. The use of three separate tumour infusion locations improved dose homogeneity compared to a single infusion location as a result of a more uniform radioactivity distribution. An improved doseresponse correlation was obtained when using EUD calculations based on a generic set of radiobiological parameters (R 2 = 0.84) than when using average tumour absorbed dose (R 2 = 0.22). Varying radiobiological parameter values over ranges commonly used for all types of tumours showed little effect on EUD calculations which suggests that individualized parameter use is of little significance as long as the intratumoural dose heterogeneity is taken into consideration in the dose-response relationship. The improved predictability achieved when using EUD calculations for this cancer therapy modality may be useful for treatment planning and evaluation.

Nuclear imaging of liposomal drug delivery systems: A critical review of radiolabelling methods and applications in nanomedicine

“…In a radionuclide therapy model, Hrycushko et al. found that taking into account intratumoural heterogeneity for absorbed-dose calculations after local delivery of 186 Re-labelled liposomes provided better correlation with tumour shrinkage than using the average tumour absorbed dose [303]. While such precise intratumoural distribution analysis is non-trivial, it is expected that future technological improvements will simplify this type of analysis, and will allow to correlate for example the spatial distribution of a radiolabelled drug with the therapeutic outcome with better accuracy than simply using the total amount of drug delivered to the tumour.…”

Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific targeted radionuclide therapy dosimetry using CLR1404

“…Conversely, the MRI contour for Patient 5 indicated slightly less dose homogeneity than the PET-based contours because the MRI DVH had a larger low dose shoulder. Accurate qualification of the tumor dose homogeneity is important because non-uniform dose distributions in TRT can have significant clinical implications for the treatment response and toxicity (O’Donoghue, 1999, Amro et al, 2010, Hanaoka et al, 2014, Hrycushko et al, 2011). Specifically, one study by Hrycushko et al (2011), investigating the impact of 186 Re-liposome dose heterogeneity in head and neck squamous cell carcinoma mouse xenografts, found that cold spots resulted in reduced tumor control (i.e.…”

“…Accurate qualification of the tumor dose homogeneity is important because non-uniform dose distributions in TRT can have significant clinical implications for the treatment response and toxicity (O’Donoghue, 1999, Amro et al, 2010, Hanaoka et al, 2014, Hrycushko et al, 2011). Specifically, one study by Hrycushko et al (2011), investigating the impact of 186 Re-liposome dose heterogeneity in head and neck squamous cell carcinoma mouse xenografts, found that cold spots resulted in reduced tumor control (i.e. tumor shrinkage) analogous to the results seen for human patients undergoing external beam radiotherapy (Niemierko and Goitein, 1991, Tomé and Fowler, 2002).…”

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

“…Based on biodistribution results in rats, dose distributions were modeled and radiobiological indexes determined, following direct injection of 188 Re-liposomes into the lumpectomy cavity (215, 216). The same group also carried out a similar work with head and neck squamous cell carcinoma, following direct intratumoral infusion of 99m Tc-labeled liposomes (217, 218). These theoretical results would need to be confirmed in vivo .…”