Publications [#65216] of Michael R. Zalutsky

Papers Published

1. Hauck, M.L. and Zalutsky, M.R., Enhanced tumour uptake of radiolabelled antibodies by hyperthermia. Part I. Timing of injection relative to hyperthermia, Int. J. Hyperth. (UK), vol. 21 no. 1 (2005), pp. 1 - 11 [02656730410001695906]
   (last updated on 2007/04/15)

   Abstract:
   Improving drug and macromolecular delivery of anticancer agents to tumours results in greater efficacy without increased toxicity. The current study was undertaken to assess the effects of the timing of injection of tumour specific and nonspecific monoclonal antibodies (mAbs) relative to a hyperthermia treatment on tumour and normal tissue uptake. Using a local hyperthermia protocol of 45 min at 43°C, uptake in tumour and normal tissues was measured at 1, 4, 12, 24, 48 and 72 h after injection. An antitenascin chimeric mAb, ch81C6, served as the specific mAb in a D-54 MG glioma xenograft mouse model. The chimeric mAb chTPS3.2 served as the control. A five-to-eight-fold increase in uptake of the tumour-targeted mAb was achieved in the heated tumours when compared with the nonheated tumours at 1 h. Differences in absolute tumour uptake of the specific mAb between the mice injected prior to hyperthermia and mice injected posthyperthermia were seen only at 1 and 12h. The median uptakes in the tumours of mice injected preheat were 25%ID/g at 1 h and 43.5%ID/g at 12h, while in the animals injected posthyperthermia the median uptakes were 45.5%ID/g and 80.2%ID/g, respectively. Blood levels of both the specific and nonspecific mAbs were consistently higher over the initial 12 h period in the mice injected posthyperthermia. Normal tissue uptake was also increased at most time points in the mice injected posthyperthermia. The clinical importance of the differences in specific mAb uptake in tumour detected statistically at 1 and 12 h is questionable, given the highly variable nature of mAb uptake in vivo. Tumour targeting mAbs administered in combination with heat may be injected either prior to or immediately following hyperthermia treatment, with the expectation that levels of uptake in tumour will be relatively equivalent. Absolute normal tissue levels will be higher in patients receiving the mAb posthyperthermia

   Keywords:
   blood;cancer;drug delivery systems;drugs;hyperthermia;proteins;tumours;