Science handbook

1999 handbook for the faculty of Scienc

Whose national emergency? Caboolture and Kirribili? or Milikapiti and Mutitjulu?

Keynote Address - Ms Marion Scrymgour MLA Member for Arafura, Northern Territory Government. Other Speakers - Professor Gavin Brown AO FAA, Vice-Chancellor and Principal, University of Sydney; Mr Neville Perkins OAM, Master of Ceremonies; Mr Charles Madden, Welcome to country; Ms Michelle Blanchard, Acting Director, Koori Centre; Mr Nicholas Beeton, Ms Kerry Wallace-Massone, Ms Jade Swan Prize winners, Dr Charles Perkins AO Annual Memorial Prize

PET imaging for characterization of head and neck tumors.

Contains fulltext : 125603.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 17 april 2014Promotores : Kaanders, J.H.A.M., Boerman, O.C., Oyen, W.J.G. Co-promotor : Bussink, J

Quantitative Imaging of the Hypoxia-Related Marker CAIX in Head and Neck Squamous Cell Carcinoma Xenograft Models

Contains fulltext : 201348.pdf (publisher's version ) (Open Access

In response to "Histopathologic validation of 3'-deoxy-3'-(18)F-fluorothymidine PET for detecting tumour repopulation during fractionated radiotherapy in human FaDu squamous cell carcinoma in nude mice"

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Imaging carbonic anhydrase IX as a method for monitoring hypoxia-related radioresistance in preclinical head and neck cancer models

BACKGROUND AND PURPOSE: Tumor hypoxia is an important cause of radioresistance and is associated with poor outcome. SPECT (Single-photon emission computed tomography) imaging enables visualizing tumor characteristics. We investigated the SPECT-radiotracer [(111)In]-girentuximab-F(ab’)(2) to image Carbonic Anhydrase IX (CAIX), an enzyme upregulated under hypoxic conditions. MATERIALS AND METHODS: Athymic mice with subcutaneous FaDu or SCCNij202 head and neck squamous cell carcinoma (HNSCC) xenografts were treated with atovaquone or were housed in a hypoxic chamber (8% O(2)). Next, [(111)In]-girentuximab-F(ab’)(2) was injected and 24 h later mice were euthanized for ex vivo biodistribution, autoradiography of the tumor, and immunohistochemical staining of the tumor. Tumor sections were analyzed for hypoxia, CAIX expression, vessels, and perfusion. Also, the effect of atovaquone on microSPECT scans was determined in the FaDu model. RESULTS: Atovaquone decreased CAIX expression by 69% (p = 0.017) compared with control tumors in FaDu, while in the SCCNij202 tumors no difference was observed. Hypoxic breathing did not increase CAIX expression or hypoxia staining in either tumor model, but did affect the necrotic tumor fraction. Ex vivo tracer uptake in the atovaquone treated group did not differ significantly from the control group, despite the difference in CAIX expression. Furthermore, SPECT imaging with [(111)In]-girentuximab-F(ab’)(2) did not discriminate atovaquone-treated versus control tumors. CONCLUSION: Atovaquone decreased CAIX expression only in the FaDu tumor model. [(111)In]-girentuximab-F(ab’)(2) specifically targets CAIX-expressing areas in HNSCC xenografts, but differences in vessel density and necrosis most likely affected tracer uptake in the tumors and therefore complicated quantification of changes in CAIX expression

Imaging of Epidermal Growth Factor Receptor Expression in Head and Neck Cancer with SPECT/CT and 111In-Labeled Cetuximab-F(ab')2

Item does not contain fulltextCombined treatment of advanced head and neck squamous cell carcinomas (HNSCC) with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor cetuximab improves clinical outcome in comparison to radiotherapy alone but is effective only in a few cases. To select those patients most likely to benefit from EGFR inhibition, it can be advantageous to quantify the tumor EGFR status before and possibly during therapy. The aim of this study was to develop and characterize the (111)In-cetuximab-F(ab')2 tracer to image EGFR targeting in vivo. METHODS: The affinity and internalization kinetics of (111)In-cetuximab-F(ab')2 were determined in vitro. The optimal protein-fragment dose for imaging was determined in nude mice with a subcutaneous head and neck carcinoma model (FaDu). Mice with FaDu tumors were imaged using ultra-high-resolution SPECT with (111)In-cetuximab-F(ab')2 or (111)In-cetuximab IgG at 4, 24, 48, and 168 h after injection. Tumor tracer uptake was determined on micro-SPECT and autoradiography images of tumor sections. Immunohistochemical staining was used to analyze EGFR expression in the tumor. RESULTS: In vitro, more than 50% of (111)In-cetuximab-F(ab')2 was internalized into FaDu cells within 24 h. The half maximal inhibitory concentration (IC50) of (111)In-cetuximab-F(ab')2 and (111)In-cetuximab was similar: 0.42 +/- 0.16 nM versus 0.28 +/- 0.14 nM, respectively. The protein dose-escalation study showed that the highest uptake of (111)In-cetuximab-F(ab')2 in tumors was obtained at doses of 10 mug/mouse or less (13.5 +/- 5.2 percentage injected dose per gram [%ID/g]). Tumor uptake of (111)In-cetuximab was significantly higher (26.9 +/- 3.3 %ID/g, P < 0.01). However, because of rapid blood clearance, tumor-to-blood ratios at 24 h after injection were significantly higher for (111)In-cetuximab-F(ab')2 (31.4 +/- 3.8 vs. 1.7 +/- 0.2, respectively; P < 0.001). The intratumoral distribution of (111)In-cetuximab-F(ab')2 correlated well with the immunohistochemical distribution of EGFR (r = 0.64 +/- 0.06, P < 0.0001). micro-SPECT images of (111)In-cetuximab-F(ab')2 clearly showed preferential uptake in the tumor from 4 h onward, with superior tumor-to-background contrast at 24 h, compared with (111)In-cetuximab (107.0 +/- 17.0 vs. 69.7 +/- 3.9, respectively; P < 0.05). CONCLUSION: (111)In-cetuximab-F(ab')2 displays higher tumor-to-blood ratios early after injection than (111)In-cetuximab in an HNSCC model, making it more suitable for EGFR visualization and potentially for selecting patients for treatment with EGFR inhibitors

111In-cetuximab-F(ab')2 SPECT imaging for quantification of accessible epidermal growth factor receptors (EGFR) in HNSCC xenografts

BACKGROUND AND PURPOSE: Immunohistochemical epidermal growth factor receptor (EGFR) expression does not correlate with treatment response in head and neck squamous cell carcinomas (HNSCC). Aim was to apply the tracer (111)In-cetuximab-F(ab')2 for EGFR microSPECT imaging and to investigate if tracer uptake correlated with response to EGFR-inhibition by cetuximab in HNSCC xenografts. Usage of F(ab)2 fragments allows for shorter interval between tracer injection and imaging. MATERIALS AND METHODS: Mice with HNSCC xenografts, SCCNij202, 153, 185 and 167 were imaged with microSPECT using (111)In-cetuximab-F(ab')2. Subsequently, tumors were analyzed by autoradiography and immunohistochemistry and tracer concentration was determined. Tumor uptake was correlated with previously assessed response to cetuximab treatment. RESULTS: MicroSPECT imaging showed preferential uptake in HNSCC xenografts. Tumor-to-liver ratios were 3.1 +/- 0.2 (SCCNij202), 2.8 +/- 0.4 (SCCNij153), 2.0 +/- 0.8 (SCCNij185), 2.0 +/- 0.4 (SCCNij167). Immunohistochemical EGFR fractions (fEGFR) differed significantly between xenografts; 0.77 +/- 0.07 (SCCNij202), 0.66 +/- 0.11 (SCCNij153), 0.57 +/- 0.19 (SCCNij185), 0.16 +/- 0.10 (SCCNij167) (p < 0.001). Tumor fEGFR correlated with (111)In-cetuximab-F(ab')2 tumor uptake (r = 0.6, p < 0.01) and tracer autoradiography (r = 0.7, p < 0.0001). Tumor uptake of (111)In-cetuximab-F(ab')2 was proportionally associated with cetuximab treatment response in three out of four xenograft models. CONCLUSION: (111)In-cetuximab-F(ab')2 showed good tumor-to-background contrast on microSPECT imaging, allowing noninvasive assessment of EGFR expression in vivo, and possibly evaluation of treatment response to EGFR-inhibition