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8. Supplementary Figure Captions from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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9. Supplementary Figure 1 from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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10. Supplementary Figure 2 from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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11. Supplementary Figure 6 from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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12. Supplementary Figure 5 from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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13. Supplementary Figure 3 from Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, primary, Baker, Lauren C.J., primary, Schmidt, Maria A., primary, Wong, Kee H., primary, Riddell, Angela M., primary, Koh, Dow-Mu, primary, Dunlop, Alex, primary, Mcquaid, Dualta, primary, d'Arcy, James A., primary, Bhide, Shreerang A., primary, Harrington, Kevin J., primary, Nutting, Christopher M., primary, Hopkinson, Georgina, primary, Richardson, Cheryl, primary, Box, Carol, primary, Eccles, Suzanne A., primary, Leach, Martin O., primary, Robinson, Simon P., primary, and Newbold, Kate L., primary

Published
2023
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29. The effect of FASN inhibition on the growth and metabolism of a cisplatin‐resistant ovarian carcinoma model

Author

Papaevangelou, Efthymia, Almeida, Gilberto S., Box, Carol, deSouza, Nandita M., and Chung, Yuen‐Li

Subjects
Orlistat, Ovarian Neoplasms, MRS, Glutamine, Fatty Acids, Antineoplastic Agents, FASN, Fatty Acid Synthase, Type I, Disease Models, Animal, Mice, ovarian cancer, Drug Resistance, Neoplasm, Cell Line, Tumor, Animals, Humans, Female, cisplatin resistance, Cisplatin, Cancer Therapy and Prevention, metabolism, Oxidation-Reduction
Abstract

Overexpression of fatty acid synthase (FASN), a key regulator of the de novo synthesis of fatty acids, has been demonstrated in a variety of cancers and is associated with poor prognosis and increased multidrug resistance. Inhibition of FASN with the anti‐obesity drug orlistat has been shown to have significant anti‐tumourigenic effects in many cancers, notably breast and prostate. In our study, we investigated whether FASN inhibition using orlistat is an effective adjunctive treatment for ovarian cancers that have become platinum resistant using a cisplatin‐resistant ovarian tumour xenograft model in mice. Mice were treated with orlistat or cisplatin or a combination and metabolite analysis and histopathology were performed on the tumours ex vivo. Orlistat decreased tumour fatty acid metabolism by inhibiting FASN, cisplatin reduced fatty acid β‐oxidation, and combination treatment delayed tumour growth and induced apoptotic and necrotic cell death in cisplatin‐resistant ovarian cancer cells over and above that with either treatment alone. Combination treatment also decreased glutamine metabolism, nucleotide and glutathione biosynthesis and fatty acid β‐oxidation. Our data suggest that orlistat chemosensitised platinum‐resistant ovarian cancer to treatment with platinum and resulted in enhanced efficacy., What's new? Targeting metabolic dependencies of tumor cells has emerged as a promising new therapeutic approach. Here the authors used an approved anti‐obesity drug, orlistat, as an adjuvant treatment for platinum‐resistant ovarian cancer. They show that in mice addition of orlistat re‐sensitises tumors to cisplatin therapy and speculate that the combination of orlistat and cisplatin could be used clinically to treat patients with platinum‐refractory ovarian cancer.

Published
2018

32. Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

Author

Nimalasena, Samantha, primary, Gothard, Lone, additional, Anbalagan, Selvakumar, additional, Allen, Steven, additional, Sinnett, Victoria, additional, Mohammed, Kabir, additional, Kothari, Gargi, additional, Musallam, Annette, additional, Lucy, Claire, additional, Yu, Sheng, additional, Nayamundanda, Gift, additional, Kirby, Anna, additional, Ross, Gill, additional, Sawyer, Elinor, additional, Castell, Fiona, additional, Cleator, Susan, additional, Locke, Imogen, additional, Tait, Diana, additional, Westbury, Charlotte, additional, Wolstenholme, Virginia, additional, Box, Carol, additional, Robinson, Simon P., additional, Yarnold, John, additional, and Somaiah, Navita, additional

Published
2020
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34. Non-invasive Imaging of Cycling Hypoxia in Head & Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, Welsh, Liam, Baker, Lauren C.J., Schmidt, Maria A., Wong, Kee H., Riddell, Angela M., Koh, Dow-Mu, Dunlop, Alex, Mcquaid, Dualta, d’Arcy, James A., Bhide, Shreerang A., Harrington, Kevin J., Nutting, Christopher M., Hopkinson, Georgina, Richardson, Cheryl, Box, Carol, Eccles, Suzanne A., Leach, Martin O., Robinson, Simon P., and Newbold, Kate L.

Subjects
Male, Neovascularization, Pathologic, Squamous Cell Carcinoma of Head and Neck, Contrast Media, Magnetic Resonance Imaging, Radiation Tolerance, Xenograft Model Antitumor Assays, Article, Cell Hypoxia, Mice, Treatment Outcome, Head and Neck Neoplasms, Nitroimidazoles, Cell Line, Tumor, Carcinoma, Squamous Cell, Animals, Humans, Female, Lymph Nodes
Published
2017

35. International Society for Therapeutic Ultrasound Conference 2016

Author

Fowlkes, Brian, Ghanouni, Pejman, Sanghvi, Narendra, Coussios, Constantin, Lyon, Paul C., Gray, Michael, Mannaris, Christophoros, Victor, Marie de Saint, Stride, Eleanor, Cleveland, Robin, Carlisle, Robert, Wu, Feng, Middleton, Mark, Gleeson, Fergus, Aubry, Jean-Franҫois, Pauly, Kim Butts, Moonen, Chrit, Vortman, Jacob, Sharabi, Shirley, Daniels, Dianne, Last, David, Guez, David, Levy, Yoav, Volovick, Alexander, Grinfeld, Javier, Rachmilevich, Itay, Amar, Talia, Zibly, Zion, Mardor, Yael, Harnof, Sagi, Plaksin, Michael, Weissler, Yoni, Shoham, Shy, Kimmel, Eitan, Naor, Omer, Farah, Nairouz, Paeng, Dong-Guk, Xu, Zhiyuan, Snell, John, Quigg, Anders H., Eames, Matthew, Jin, Changzhu, Everstine, Ashli C., Sheehan, Jason P., Lopes, Beatriz S., Kassell, Neal, Looi, Thomas, Khokhlova, Vera, Mougenot, Charles, Hynynen, Kullervo, Drake, James, Slayton, Michael, Amodei, Richard C., Compton, Keegan, McNelly, Ashley, Latt, Daniel, Kearney, John, Melodelima, David, Dupre, Aurelien, Chen, Yao, Perol, David, Vincenot, Jeremy, Chapelon, Jean-Yves, Rivoire, Michel, Guo, Wei, Ren, Guoxin, Shen, Guofeng, Neidrauer, Michael, Zubkov, Leonid, Weingarten, Michael S., Margolis, David J., Lewin, Peter A., McDannold, Nathan, Sutton, Jonathan, Vykhodtseva, Natalia, Livingstone, Margaret, Kobus, Thiele, Zhang, Yong-Zhi, Schwartz, Michael, Huang, Yuexi, Lipsman, Nir, Jain, Jennifer, Chapman, Martin, Sankar, Tejas, Lozano, Andres, Yeung, Robert, Damianou, Christakis, Papadopoulos, Nikolaos, Brokman, Omer, Zadicario, Eyal, Brenner, Ori, Castel, David, Wu, Shih-Ying, Grondin, Julien, Zheng, Wenlan, Heidmann, Marc, Karakatsani, Maria Eleni, Sánchez, Carlos J. Sierra, Ferrera, Vincent, Konofagou, Elisa E., Yiannakou, Marinos, Cho, HongSeok, Lee, Hwayoun, Han, Mun, Choi, Jong-Ryul, Lee, Taekwan, Ahn, Sanghyun, Chang, Yongmin, Park, Juyoung, Ellens, Nicholas, Partanen, Ari, Farahani, Keyvan, Airan, Raag, Carpentier, Alexandre, Canney, Michael, Vignot, Alexandre, Lafon, Cyril, Delattre, Jean-yves, Idbaih, Ahmed, Odéen, Henrik, Bolster, Bradley, Jeong, Eun Kee, Parker, Dennis L., Gaur, Pooja, Feng, Xue, Fielden, Samuel, Meyer, Craig, Werner, Beat, Grissom, William, Marx, Michael, Weber, Hans, Taviani, Valentina, Hargreaves, Brian, Tanaka, Jun, Kikuchi, Kentaro, Ishijima, Ayumu, Azuma, Takashi, Minamihata, Kosuke, Yamaguchi, Satoshi, Nagamune, Teruyuki, Sakuma, Ichiro, Takagi, Shu, Santin, Mathieu D., Marsac, Laurent, Maimbourg, Guillaume, Monfort, Morgane, Larrat, Benoit, François, Chantal, Lehéricy, Stéphane, Tanter, Mickael, Samiotaki, Gesthimani, Wang, Shutao, Acosta, Camilo, Feinberg, Eliza R., Kovacs, Zsofia I., Tu, Tsang-Wei, Papadakis, Georgios Z., Reid, William C., Hammoud, Dima A., Frank, Joseph A., Kovacs, Zsofia i., Kim, Saejeong, Jikaria, Neekita, Bresler, Michele, Qureshi, Farhan, Xia, Jingjing, Tsui, Po-Shiang, Liu, Hao-Li, Plata, Juan C., Sveinsson, Bragi, Salgaonkar, Vasant A., Adams, Matthew, Diederich, Chris, Ozhinsky, Eugene, Bucknor, Matthew D., Rieke, Viola, Mikhail, Andrew, Severance, Lauren, Negussie, Ayele H., Wood, Bradford, de Greef, Martijn, Schubert, Gerald, Ries, Mario, Poorman, Megan E., Dockery, Mary, Chaplin, Vandiver, Dudzinski, Stephanie O., Spears, Ryan, Caskey, Charles, Giorgio, Todd, Costa, Marcia M., Papaevangelou, Efthymia, Shah, Anant, Rivens, Ian, Box, Carol, Bamber, Jeff, ter Haar, Gail, Burks, Scott R., Nagle, Matthew, Nguyen, Ben, Milo, Blerta, Le, Nhan M., Song, Shaozhen, Zhou, Kanheng, Nabi, Ghulam, Huang, Zhihong, Ben-Ezra, Shmuel, Rosen, Shani, Mihcin, Senay, Strehlow, Jan, Karakitsios, Ioannis, Le, Nhan, Schwenke, Michael, Demedts, Daniel, Prentice, Paul, Haase, Sabrina, Preusser, Tobias, Melzer, Andreas, Mestas, Jean-Louis, Chettab, Kamel, Gomez, Gustavo Stadthagen, Dumontet, Charles, Werle, Bettina, Marquet, Fabrice, Bour, Pierre, Vaillant, Fanny, Amraoui, Sana, Dubois, Rémi, Ritter, Philippe, Haïssaguerre, Michel, Hocini, Mélèze, Bernus, Olivier, Quesson, Bruno, Livneh, Amit, Adam, Dan, Robin, Justine, Arnal, Bastien, Fink, Mathias, Pernot, Mathieu, Khokhlova, Tatiana D., Schade, George R., Wang, Yak-Nam, Kreider, Wayne, Simon, Julianna, Starr, Frank, Karzova, Maria, Maxwell, Adam, Bailey, Michael R., Lundt, Jonathan E., Allen, Steven P., Sukovich, Jonathan R., Hall, Timothy, Xu, Zhen, May, Philip, Lin, Daniel W., Constans, Charlotte, Deffieux, Thomas, Aubry, Jean-Francois, Park, Eun-Joo, Ahn, Yun Deok, Kang, Soo Yeon, Park, Dong-Hyuk, Lee, Jae Young, Vidal-Jove, J., Perich, E., Ruiz, A., Jaen, A., Eres, N., del Castillo, M. Alvarez, Myers, Rachel, Kwan, James, Coviello, Christian, Rowe, Cliff, Crake, Calum, Finn, Sean, Jackson, Edward, Pouliopoulos, Antonios, Li, Caiqin, Tinguely, Marc, Tang, Meng-Xing, Garbin, Valeria, Choi, James J., Folkes, Lisa, Stratford, Michael, Nwokeoha, Sandra, Li, Tong, Farr, Navid, D’Andrea, Samantha, Gravelle, Kayla, Chen, Hong, Lee, Donghoon, Hwang, Joo Ha, Tardoski, Sophie, Ngo, Jacqueline, Gineyts, Evelyne, Roux, Jean-Pau, Clézardin, Philippe, Conti, Allegra, Magnin, Rémi, Gerstenmayer, Matthieu, Lux, François, Tillement, Olivier, Mériaux, Sébastien, Penna, Stefania Della, Romani, Gian Luca, Dumont, Erik, Sun, Tao, Power, Chanikarn, Miller, Eric, Sapozhnikov, Oleg, Tsysar, Sergey, Yuldashev, Petr V., Svet, Victor, Li, Dongli, Pellegrino, Antonio, Petrinic, Nik, Siviour, Clive, Jerusalem, Antoine, Yuldashev, Peter V., Cunitz, Bryan W., Dunmire, Barbrina, Inserra, Claude, Guedra, Matthieu, Mauger, Cyril, Gilles, Bruno, Solovchuk, Maxim, Sheu, Tony W. H., Thiriet, Marc, Zhou, Yufeng, Neufeld, Esra, Baumgartner, Christian, Payne, Davnah, Kyriakou, Adamos, Kuster, Niels, Xiao, Xu, McLeod, Helen, Dillon, Christopher, Payne, Allison, Khokhova, Vera A., Sinilshchikov, Ilya, Andriyakhina, Yulia, Rybyanets, Andrey, Shvetsova, Natalia, Berkovich, Alex, Shvetsov, Igor, Shaw, Caroline J., Civale, John, Giussani, Dino, Lees, Christoph, Ozenne, Valery, Toupin, Solenn, Salgaonkar, Vasant, Kaye, Elena, Monette, Sebastien, Maybody, Majid, Srimathveeravalli, Govindarajan, Solomon, Stephen, Gulati, Amitabh, Bezzi, Mario, Jenne, Jürgen W., Lango, Thomas, Müller, Michael, Sat, Giora, Tanner, Christine, Zangos, Stephan, Günther, Matthias, Dinh, Au Hoang, Niaf, Emilie, Bratan, Flavie, Guillen, Nicolas, Souchon, Rémi, Lartizien, Carole, Crouzet, Sebastien, Rouviere, Olivier, Han, Yang, Payen, Thomas, Palermo, Carmine, Sastra, Steve, Olive, Kenneth, van Breugel, Johanna M., van den Bosch, Maurice A., Fellah, Benjamin, Le Bihan, Denis, Hernandez-Garcia, Luis, Cain, Charles A., Lyka, Erasmia, Elbes, Delphine, Li, Chunhui, Tamano, Satoshi, Jimbo, Hayato, Yoshizawa, Shin, Fujiwara, Keisuke, Itani, Kazunori, Umemura, Shin-ichiro, Stoianovici, Dan, Zaini, Zulfadhli, Takagi, Ryo, Zong, Shenyan, Watkins, Ron, Pascal-Tenorio, Aurea, Jones, Peter, Butts-Pauly, Kim, Bouley, Donna, Chen, Yazhu, Lin, Chung-Yin, Hsieh, Han-Yi, Wei, Kuo-Chen, Garnier, Camille, Renault, Gilles, Seifabadi, Reza, Wilson, Emmanuel, Eranki, Avinash, Kim, Peter, Lübke, Dennis, Huber, Peter, Georgii, Joachim, Dresky, Caroline V., Haller, Julian, Yarmolenko, Pavel, Sharma, Karun, Celik, Haydar, Li, Guofeng, Qiu, Weibao, Zheng, Hairong, Tsai, Meng-Yen, Chu, Po-Chun, Webb, Taylor, Vyas, Urvi, Walker, Matthew, Zhong, Jidan, Waspe, Adam C., Hodaie, Mojgan, Yang, Feng-Yi, Huang, Sin-Luo, Zur, Yuval, Assif, Benny, Aurup, Christian, Kamimura, Hermes, Carneiro, Antonio A., Rothlübbers, Sven, Schwaab, Julia, Houston, Graeme, Azhari, Haim, Weiss, Noam, Sosna, Jacob, Goldberg, S. Nahum, Barrere, Victor, Jang, Kee W., Lewis, Bobbi, Wang, Xiaotong, Suomi, Visa, Edwards, David, Larrabee, Zahary, Hananel, Arik, Rafaely, Boaz, Debbiny, Rasha Elaimy, Dekel, Carmel Zeltser, Assa, Michael, Menikou, George, Mouratidis, Petros, Pineda-Pardo, José A., de Pedro, Marta Del Álamo, Martinez, Raul, Hernandez, Frida, Casas, Silvia, Oliver, Carlos, Pastor, Patricia, Vela, Lidia, Obeso, Jose, Greillier, Paul, Zorgani, Ali, Catheline, Stefan, Solovov, Vyacheslav, Vozdvizhenskiy, Michael O., Orlov, Andrew E., Wu, Chueh-Hung, Sun, Ming-Kuan, Shih, Tiffany T., Chen, Wen-Shiang, Prieur, Fabrice, Pillon, Arnaud, Cartron, Valerie, Cebe, Patrick, Chansard, Nathalie, Lafond, Maxime, Seya, Pauline Muleki, Bera, Jean-Christophe, Boissenot, Tanguy, Fattal, Elias, Bordat, Alexandre, Chacun, Helene, Guetin, Claire, Tsapis, Nicolas, Maruyama, Kazuo, Unga, Johan, Suzuki, Ryo, Fant, Cécile, Rogez, Bernadette, Afadzi, Mercy, Myhre, Ola Finneng, Vea, Siri, Bjørkøy, Astrid, Yemane, Petros Tesfamichael, van Wamel, Annemieke, Berg, Sigrid, Hansen, Rune, Angelsen, Bjørn, and Davies, Catharina

Subjects
Meeting Abstracts
Published
2017

36. Evaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma

Author

Baker, Lauren C. J., primary, Sikka, Arti, additional, Price, Jonathan M., additional, Boult, Jessica K. R., additional, Lepicard, Elise Y., additional, Box, Gary, additional, Jamin, Yann, additional, Spinks, Terry J., additional, Kramer-Marek, Gabriela, additional, Leach, Martin O., additional, Eccles, Suzanne A., additional, Box, Carol, additional, and Robinson, Simon P., additional

Published
2018
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39. Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Author

Panek, Rafal, primary, Welsh, Liam, additional, Baker, Lauren C.J., additional, Schmidt, Maria A., additional, Wong, Kee H., additional, Riddell, Angela M., additional, Koh, Dow-Mu, additional, Dunlop, Alex, additional, Mcquaid, Dualta, additional, d'Arcy, James A., additional, Bhide, Shreerang A., additional, Harrington, Kevin J., additional, Nutting, Christopher M., additional, Hopkinson, Georgina, additional, Richardson, Cheryl, additional, Box, Carol, additional, Eccles, Suzanne A., additional, Leach, Martin O., additional, Robinson, Simon P., additional, and Newbold, Kate L., additional

Published
2017
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40. MOESM1 of Flexible Targeting of ErbB Dimers That Drive Tumorigenesis by Using Genetically Engineered T Cells

Author

Davies, David, Foster, Julie, Stegen, Sjoukje Van Der, Parente-Pereira, Ana, Chiapero-Stanke, Laura, Delinassios, George, Burbridge, Sophie, Kao, Vincent, Liu, Zhe, Bosshard-Carter, Leticia, Schalkwyk, May Van, Box, Carol, Eccles, Suzanne, Mather, Stephen, Wilkie, Scott, and Maher, John

Abstract

Supplementary material, approximately 673 KB.

Published
2012
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44. Pre-clinical quantitative imaging and mouse-specific dosimetry for In-labelled radiotracers.

Author

Denis-Bacelar, Ana, Cronin, Sarah, Da Pieve, Chiara, Paul, Rowena, Eccles, Sue, Spinks, Terence, Box, Carol, Hall, Adrian, Sosabowski, Jane, Kramer-Marek, Gabriela, and Flux, Glenn

Subjects
RADIOACTIVE tracers, RADIATION dosimetry, DIAGNOSTIC imaging, LABORATORY rats, FEASIBILITY studies
Abstract

Background: Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of In-labelled radiotracers. Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice were injected with In-labelled HER2-targeting monoclonal antibodies (mAbs) (range 5.58-8.52 MBq). Sequential SPECT imaging up to 197 h post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner. Mice were culled for quantitative analysis of biodistribution studies. The tumour activity, mass and percentage of injected activity per gram of tissue (%IA/g) were calculated at the final scan time point and compared to the values determined from the biodistribution data. Delivered In-labelled mAbs tumour absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for In. Results: For the sphere sizes investigated (volume 0.03-1.17 ml), the calibration factor varied by a factor of 3.7, whilst for the range of tumour masses in the mice (41-232 mg), the calibration factor changed by a factor of 2.5. Comparisons between the mice imaging and the biodistribution results showed a statistically significant correlation for the tumour activity ( r = 0.999, P < 0.0001) and the tumour mass calculations ( r = 0.977, P = 0.0008), whilst no correlation was found for the %IA/g ( r = 0.521, P = 0.29). Median tumour-absorbed doses per injected activity of 52 cGy/MBq (range 36-69 cGy/MBq) and 649 cGy/MBq (range 441-950 cGy/MBq) were delivered by In-labelled mAbs and extrapolated for Y-labelled mAbs, respectively. Conclusions: This study demonstrates the need for multidisciplinary efforts to standardise imaging and dosimetry protocols in pre-clinical imaging. Accurate image quantification can improve the calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be used to estimate the injected activities required for therapeutic studies, potentially reducing the number of animals used. [ABSTRACT FROM AUTHOR]

Published
2016
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