A Tracer Dose of Technetium-99m–Labeled Liposomes Can Estimate the Effect of Hyperthermia on Intratumoral Doxil Extravasation

Abstract

Purpose: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m ( 99m Tc)^labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experimental Design: Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m ( 99m Tc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99m Tc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Results: Intratumoral extravasation of the 99m Tc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. Conclusions: The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Radio‐Labeled Nanoparticles for Biomedical Imaging

“…mice were injected with either the 99m Tc-labeled liposome, Doxil, or both with subsequent quantification of tumor delivery post-hyperthermia treatment. This allowed visualization of the drug's effectiveness in reaching its target site [54]. In another study, the pharmacokinetics of intratumoral injections of liposomal-based drugs was quantified with 99m Tc-labeled liposomes.…”

Correlation between radioactivity and chemotherapeutics of the 111In-VNB-liposome in pharmacokinetics and biodistribution in rats

“…38 The combined therapeutic efficacy of the 111 In-VNB-liposome has been evaluated in colorectal carcinoma-bearing mice. 22,23 Indium-111 is a radionuclide commonly used for scintigraphic imaging (t 1/2 2.81 days, 172 and 247 keV photon emission), emitting 14.7 Auger electrons (mean energy 0.46 keV) on average per decay, and may also be suitable for radiotherapy.…”

Combination Radiofrequency Ablation and Intravenous Radiolabeled Liposomal Doxorubicin: Imaging and Quantification of Increased Drug Delivery to Tumors

“…Furthermore, because the imaging and tissue counting results correlated closely with the drug concentration in tumors, our study results also demonstrate that the increased drug delivery that occurs with combination therapy can be not only depicted but also quantifi ed with noninvasive imaging. This quantification could lead to a future application of imaging-based chemical dosimetry ( 43,44 ).…”