@article{hauck_zalutsky_2005, title={Enhanced tumour uptake of radiolabelled antibodies by hyperthermia. Part II: Application of the thermal equivalency equation}, volume={21}, ISSN={["1464-5157"]}, DOI={10.1080/02656730400011032}, abstractNote={Clinical application of local hyperthermia as a means for modulating drug and macro-molecular tumour uptake have been slow to develop, due in part to the difficulty in designing and comparing heating protocols. The thermal isodose formula developed by Sapareto and Dewey is used in cytotoxicity and radiosensitization hyperthermia protocols to compare different time/temperature combinations; however, its relevance to other end-points has not been evaluated. The current study was undertaken to determine whether heating protocols of different time and temperature, but predicted to be thermally equivalent by this formula, had similar effects on the tumour and normal tissue distribution of radiolabelled tumour-specific (anti-tenascin 81C6) and non-specific (anti-dansyl TPS3.2) monoclonal antibodies (mAbs). Two thermally equivalent heating protocols, 4 h at 41.8°C and 45 min at 43°C, were compared in mice with subcutaneous D54 MG human glioma xenografts. A 4-fold increase in xenograft localization of 81C6 mAb was achieved relative to that in non-heated control groups with both heating protocols. Both hyperthermia protocols also resulted in improved tumour:normal tissue ratios. However, differences in absolute tumour and normal tissue uptake were seen, suggesting that the thermal isodose formula has limited usefulness in the design and comparison of hyperthermia protocols for enhancing the tumour uptake of radiolabelled mAbs.}, number={1}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Zalutsky, MR}, year={2005}, month={Feb}, pages={13–27} } @article{hauck_zalutsky_2005, title={Enhanced tumour uptake of radiolabelled antibodies by hyperthermia: Part I: Timing of injection relative to hyperthermia}, volume={21}, ISSN={["1464-5157"]}, DOI={10.1080/02656730410001695906}, abstractNote={Improving drug and macromolecular delivery of anti-cancer 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 non-specific 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 anti-tenascin 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 non-heated tumours at 1 h. Differences in absolute tumour uptake of the specific mAb between the mice injected prior to hyperthermia and mice injected post-hyperthermia were seen only at 1 and 12 h. The median uptakes in the tumours of mice injected pre-heat were 25%ID/g at 1 h and 43.5%ID/g at 12 h, while in the animals injected post-hyperthermia the median uptakes were 45.5%ID/g and 80.2%ID/g, respectively. Blood levels of both the specific and non-specific mAbs were consistently higher over the initial 12 h period in the mice injected post-hyperthermia. Normal tissue uptake was also increased at most time points in the mice injected post-hyperthermia. 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 post-hyperthermia.}, number={1}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Zalutsky, MR}, year={2005}, month={Feb}, pages={1–11} } @article{berry_degrado_nutter_garg_breitschwerdt_spaulding_concannon_zalutsky_edward coleman_2002, title={Imaging of Pheochromocytoma in 2 dogs using p-[18F] Fluorobenzylguanidine}, volume={43}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.2002.tb01667.x}, DOI={10.1111/j.1740-8261.2002.tb01667.x}, abstractNote={ p‐[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been developed as a positron emission tomography (PET) imaging radiopharmaceutical. Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The extent of the pheochromocytoma was well documented in both dogs on the PET study. The standardized uptake values within the pheochromocytomas were greater than 25 by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG study was normal. Surgical exploration and adrenal biopsy confirmed the [18F]PFBG imaging findings in both dogs. In each dog, there was rapid blood‐pool clearance (within 10 min after intravenous administration of the [18F]PFBG), with high uptake specific within the myocardium and adrenal medulla. The results indicate that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in differentiating adrenal masses.}, number={2}, journal={Veterinary Radiology and Ultrasound}, publisher={Wiley}, author={Berry, Clifford R. and Degrado, Timothy R. and Nutter, Felicia and Garg, Pradeep K. and Breitschwerdt, Edward B. and Spaulding, Kathy and Concannon, Kevin D. and Zalutsky, Michael R. and Edward Coleman, R.}, year={2002}, month={Mar}, pages={183–186} } @article{hauck_larsen_welsh_zalutsky_1998, title={Cytotoxicity of alpha-particle emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia}, volume={77}, ISSN={["0007-0920"]}, DOI={10.1038/bjc.1998.123}, abstractNote={The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.}, number={5}, journal={BRITISH JOURNAL OF CANCER}, author={Hauck, ML and Larsen, RH and Welsh, PC and Zalutsky, MR}, year={1998}, month={Mar}, pages={753–759} } @article{hauck_zalutsky_1998, title={The effects of local hyperthermia on the catabolism of a radioiodinated chimeric monoclonal antibody}, volume={4}, journal={Clinical Cancer Research}, author={Hauck, M. L. and Zalutsky, M. R.}, year={1998}, pages={2071–2077} } @article{hauck_coffin_dodge_dewhirst_mitchell_zalutsky_1997, title={A local hyperthermia treatment which enhances antibody uptake in a glioma xenograft model does not affect tumour interstitial fluid pressure}, volume={13}, ISSN={["0265-6736"]}, DOI={10.3109/02656739709023538}, abstractNote={Solid tumours have an elevated interstitial fluid pressure (IFP) due to the lack of normal lymphatics, increased permeability of tumour vasculature and an expanding cell population within a potentially limited space. This elevated IFP has been proposed to be an important barrier to the delivery of drugs and marcromolecules. We have demonstrated that local hyperthermia (4 h, 41.8 degrees C) is capable of significantly enhancing the uptake of radiolabelled monoclonal antibodies (mAbs) in D-54 MG glioma xenografts grown subcutaneously in athymic mice. To determine if this increased uptake was attributable to alterations in the tumour IFP, pressure measurements using the wick-in-needle technique were made in tumours after hyperthermia treatment. These pressure measurements were taken at various time points from 4 to 90 h following the initiation of the hyperthermia and compared with pressures taken concurrently in untreated tumours. In addition, pressures were measured following a 2 h, 41.8 degrees C hyperthermia treatment, a protocol which does not result in elevated uptake of radiolabeled mAbs. No significant differences were seen at any time point in IFP measured in the tumours receiving either hyperthermia treatment when compared with untreated tumours. Thus, we conclude that the mechanism by which this hyperthermia regimen enhances mAb uptake in this human glioma xenograft model is not due to alternations in tumour IFP.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Coffin, DO and Dodge, RK and Dewhirst, MW and Mitchell, JB and Zalutsky, MR}, year={1997}, pages={307–316} } @article{hauck_dewhirst_bigner_zaultsky_1997, title={Local hyperthermia improves uptake of a chimeric monoclonal antibody in a subcutaneous xenograft model}, volume={3}, journal={Clinical Cancer Research}, author={Hauck, M. L. and Dewhirst, M. W. and Bigner, D. D. and Zaultsky, M. R.}, year={1997}, pages={63–70} } @article{hauck_dewhirst_zalutsky_1996, title={The effects of clinically relevant hyperthermic temperatures on the kinetic binding parameters of a monoclonal antibody}, volume={23}, ISSN={["0883-2897"]}, DOI={10.1016/0969-8051(96)00039-x}, abstractNote={Hyperthermia is a therapeutic modality under investigation for its ability to increase absolute levels of tumor uptake of radiolabeled monoclonal antibodies (MAbs). We have investigated whether hyperthermia may affect the binding parameters of MAbs. The effects of clinically relevant levels of hyperthermia on the kinetic binding parameters were investigated for 81C6, an antibody undergoing Phase I/II clinical trials for the treatment of brain tumors and neoplastic meningitis. No obvious effects of temperature in either the association or dissociation rate constants, nor in the equilibrium constants, were apparent between 37 ° and 45 °C. The improved binding stability of the bivalent form of the MAb was apparent when compared with its monovalent Fab fragment.}, number={4}, journal={NUCLEAR MEDICINE AND BIOLOGY}, author={Hauck, ML and Dewhirst, MW and Zalutsky, MR}, year={1996}, month={May}, pages={551–557} } @inbook{hauck_dewhirst_zalutsky_1995, title={Enhancement of radiolabeled monoclonal antibody uptake in tumors with local hyperthermia}, booktitle={Handbook of targeted delivery of imaging agents}, author={Hauck, M. L. and Dewhirst, M. W. and Zalutsky, M. R.}, year={1995}, pages={333–359} }