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.

Determination of urolith mineral composition is critical for management of urolithiasis in dogs and cats. Using computed tomography, urolith physical density, and hence chemical composition, can be quantified using mean beam attenuation measurements (Hounsfield units; HU). This study was designed to establish in vitro reference ranges for three types of compositionally pure uroliths retrieved from dogs. Sixty-six canine uroliths (22 uric acid, 21 calcium oxalate, 14 struvite, nine mixed or compound) were placed in a phantom array. Uroliths were scanned at 120 kVp, 200 mA, and 80 kVp, 200 mA. The region of interest (ROI) for mean HU calculation was determined using two techniques, and reference ranges were calculated for each kVp using either ROI technique. HU for urolith types of pure composition were statistically different (Wilcoxon's two-sample test, P < 0.0083 [Bonferonni correction with six comparisons for total P < 0.05]) using both ROI techniques at either kVp. Struvite uroliths were not statistically different from mixed or compound uroliths. The accuracy for determination of composition of pure uroliths ranged from 86% to 93%; the prediction accuracy for each urolith mineral type and for all uroliths in general was highest when the ROI was hand-drawn just within the visible urolith border at 80 kVp. Technique of ROI determination and kVp that yielded the highest sensitivity, specificity, and positive and negative predictive values varied for each urolith type. Therefore, in this study, HU could be used to differentiate three types of uroliths of pure mineral composition in vitro. Further studies are needed to determine the predictive value of HU in vivo.