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Cathie Long andRaymond Reilly visitReilly’s lab at theToronto GeneralResearch InstituteSo far, Phase 1 trials have confirmed that Reilly’snew treatment is safe for human use. If further trialsare successful, the therapy could be approved foruse by the end of the decadesophisticated cameras and produce imagessimilar to a CT scan. They help radiologists“see” disease, infection or injury inthe body. Different radiopharmaceuticalscan help visualize different ailments. Andearly on, Reilly began thinking aboutdesigning radiopharmaceuticals that helpdoctors detect specific kinds of cancer.His work in imaging and diagnosingdisease led to his interest in designinga radioisotope that would not onlylocate breast cancer, but also tell doctorsabout the idiosyncrasies of eachtumour. “Breast cancer is not just onedisease, though often it is treated thatway,” he says. “Tumours differ becauseof their biology. Some are more aggressivethan others.”Tumours, like cats, can be very finickyabout what they eat. Reilly wanted tounderstand the specific growth factors, orproteins, preferred by the tumours of differentbreast cancer patients. The rationalewas simple: the more informationdoctors can have about the specific dietof each tumour, the better they can usedrugs and other therapies to interferewith the diet that allows the tumour togrow unchecked.Cancer specialists were already wellaware that certain breast cancers have ahealthy appetite for the hormone estrogen.Inside these cancer cells are entitiescalled estrogen receptors, which attractthe hormone and absorb it directly intothe cancer cell nucleus, where it triggerscell growth.By the time Reilly began his doctoratework in medical biophysics in themid-1990s, these estrogen-receptor-positivebreast cancers were being successfullytreated with drugs such as tamoxifen,which inhibits the cancer cell’s abilityto take up estrogen and slows cellgrowth. But not all breast cancers arehungry for estrogen. Reilly became interestedin another kind of tumour, whichis harder to diagnose and treat. “I wantedto identify patients with a poor prognosis– those who don’t respond to tamoxifenand who might need to be treatedmore aggressively with chemotherapy,”he says.By poring over research literature,Reilly found that breast cancers thatdon’t feed off estrogen have anotherkind of receptor – one that attracts apeptide called epidermal growth factor(EGF), which is produced by the body’ssalivary glands.Reilly speculated that if he attacheda radionuclide to EGF, it would act likea homing device and take the imagingtracer directly to cancer cells with EGFreceptors. The radionuclide would causethe EGF-receptor-positive tumour tolight up on the camera image, creatingan easy, accurate and non-invasive wayto diagnose this more stubborn subsetof cancer tumours.So in 1996, Reilly was well on his wayto developing a helpful new imagingagent. Little did he know that the ficklegods of research had something a littledifferent in mind. In the midst of hisdoctoral work, Reilly attended a meetingof the Society of Nuclear Medicinewhere he noticed a research poster thatonly a radiopharmacist could love. Itdescribed how a decaying radiopharmaceutical(a form of iodine 125) coulddamage a cell’s DNA by emitting Augerelectrons. Named for the French scientistPierre Auger, who first publishedresearch on them in 1925, these electronshave a low energy and can onlytravel short distances – mere nanometres.But this is all that’s needed to wielda hefty blow within the confines of acancer cell nucleus.Reilly was dumbstruck by the enormityof the possibilities. He was usinganother Auger-electron emitting radioisotopecalled indium-111 for his work24 UNIVERSITY OF TORONTO MAGAZINE / SPRING 2006
Pinpoint DeliveryProfessor Christine Allen usesnanotechnology to ensure cancer-fightingdrugs get where they need to goMany new drugs under development havethe potential to do some good. But afterbeing swallowed or injected, they scatter,dissolve or disappear in the body beforemaking it to the site of the disease.This is where Christine Allen comes in.To get these drugs to where they’re supposedto go, the assistant professor of pharmacyat U of T is building nanoparticles toencase the drug molecules.Then she targetsthese nanoparticles to breast cancer cells inmuch the same way as her colleague RaymondReilly targets his radiotherapy. Sheattaches them to epidermal growth factorpeptides, which smuggle the nanoparticlesinside the cancer cells where the encaseddrug is released. Her creations are so smallthat she has to use an electron microscope to see them.Allen, whose doctoral work was in polymer chemistry, researchesher unique nanoparticles in a distinctly high-tech fashion. Usingsoftware that produces 3-D images, she creates virtual models ofthe new materials used to make up the particles on the supercomputerat the Molecular Design and Information Technology Centre,a leading Canadian academic bioinformatics centre devoted todrug design. Allen says the centre’s software predicts how thesematerials will interact with the drug they’reAllencarrying – helping her rule out certaindesigns and saving the inestimable expenseof making mistakes in the lab.While the work of this avowed “chemistrygeek” is still in the early stages, she isbeginning to test some of her unique compoundson animals. And she has plans tocollaborate with other scientists, such asReilly, to create hybrids of their targetedapproach.“As a material scientist workingin nanotechnology, I couldn’t be in a betterinstitution,” says Prof.Allen, who appreciatesbeing in close proximity to other like-mindedresearchers at the Leslie Dan Faculty ofPharmacy.“I can just walk down the hall andget answers to all sorts of questions.” – K. F.PHOTOGRAPHY: STEPHEN SIMEONon a new imaging agent. It occurredto him that the tool he was developingto better diagnose EGF-receptor-positivebreast cancer might actually end uptreating it.When scientists try to decode theircomplex drug delivery work to a layperson,they often use metaphors ofweaponry and stealth: the smart bombversus the carpet bomb, or the sniperversus the indiscriminate machine gun.Way back in 1996, Reilly started tothink of his potential new therapy asa Trojan Horse – a way of smugglinga deadly payload into enemy territoryunder the guise of something friendly.He had a good hunch that if he attachedindium-111 to the EGF peptide (to createan EGF conjugate) it would betaken inside EGF-receptor-positive cancercells. And he bet that when indium-111 started decaying in the cell, theemitted Auger electrons would be closeenough to the cell nucleus to irreparablydamage its DNA. In other words,he planned to exploit the cancer cells’appetite for EGF by feeding them whatPRODUCTION/PROJECTENGINEERSare you READY for an OPERATIONSLEADERSHIP ROLE?Call Tom KotsopoulosManager, Recruitment(416) 401-7516www.apotex.comSeeking highly motivated,results driven, engaging leadersfor our modern pharmaceuticalproduction facilitiesAIPOTEX NCCANADA’S PHARMACEUTICAL COMPANYWWW.MAGAZINE.UTORONTO.CA 25
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Page 8 and 9: LettersPaper of RecordWhy The Varsi
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Page 12 and 13: LeadingEdgeILLUSTRATION:WARREN HEIS
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Page 47 and 48: GreatGiftsPHOTOGRAPHY: BRUCE ZINGER
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Page 55 and 56: CalendarALUMNI EVENTSJune 1 to 4. S
Page 57 and 58: Does anyoneever stop learning?Open
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Page 61 and 62: BackLookingBY F.MICHAH RYNORInstrum
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