derivative' (HPD)ledtothe potential foruseful treatment, because ofitstumourlocalisation properties andbecause activation by light produces aphototoxic reaction whichdestroys tumourcells. Thispotential hasbeenrealised more recently because ofdevelopments inlaser andoptical fibre technology whichhaveallowed thedrugand thelight tobebrought together insuchawayastobeclinically useful. Thisisthebasis ofthe treatment knownasphotodynamic therapy (PDT).Muchexperimental andclinical workhasbeen carried outoverthepast10years anditisopportune toreview achievements andprospects atthis time. Clinical treatment is,inprinciple, verystraightforward. Abouttwoorthreedaysfollowing intravenous administration ofphotoactive drug, maximumselective concentration ofdrugintumour relative tosurrounding healthy tissue isachieved. Laser light isthendelivered tothetumourregion and cell destruction follows rapidly. Theexact mechanism whichdetermines drugconcentration intumouris notentirely clear, butmaybeimportant infuture manipulation oftherapeutic ratio. Someanimal studies haveshownlevels ofdrugintumourtissue whichareeight toninetimeshigher thanin surrounding normal tissue, butitismorecommontoachieve aratio of2:1. Themechanism oflight anddruginteraction invitro suggests thatthere isadirect cell killing effect whichpredominantly acts oncell membranes andismediated bytheproduction ofsinglet oxygen which iscytotoxic (Hilf etal., 1984). Whilethere seemstobeadirect cytotoxic effect invitro, there isastrong suggestion thatinvivo there isamajoreffect ontumourvasculature, whichveryrapidly collapses after PDT sothatthetumourcells maydieofsecondary anoxia. Thishasbeensupported inexperiments whichhaveshownthat ifthetumourisexplanted immediately after PDT,itcontinues togrow,whereas ifleft insitu itsuccumbs totheeffects ofvascular collapse (Henderson etal., 1984). Thismayitself have important implications forthetargeting oftreatment totumourstromal bloodvessels. Because ofthe almost instantaneous shutdown ofbloodflowthere israpid cell kill whichmayaffect bothtumourand normaltissue. Perhaps because ofthemodeofinjury, however, whichdiffers fromotherphysical treatments suchasheatorradiation, thenormaltissues appear tohealmuchbetter thanequivalent injury produced byother modalities andthis mayhaveanimportant bearing onthetherapeutic ratio thatcanbeachieved (Gilson etal., 1988). Thetherapeutic ratio canalsobeimproved byavoiding transmission oflight through theskinwherethere isconsiderable absorption inthefirst fewmillimetres whichcontain melanin andwherethemajoreffect islikely tooccur. Thisisnotthecaseinmucous membranes norwhenlight isdelivered interstitially byintroducing theoptical fibre belowtheskin surface. Todatethemajority ofresearch inPDT,andvirtually allclinical treatment, hasbeenperformed using HPD.Thisisanunsatisfactory mixture ofcompounds andmuchworkhasbeendirected at isolating thefractions within this mixture thataretheactive components ofPDT.Itappears thatan aggregated fraction ofhaematoporphyrin within HPD isresponsible formuchofthetumourlocalising properties andthis isthebasis ofPhotofrinII, asecond generation drug, whichisaformofHPD enriched inthelocalising fraction andwhichshowsbetter tumourlocalisation. Theabsorption spectrum ofHPD showsa large peakatapproximately 400nm.Lightofthis wavelength issopoorly penetrating, however, thatitcannot beusedtotreat tumours morethan1or 2mm thick. Forthis reason, 630nm(red) light isusually usedtoactivate thedrugandischosen as being thebestcompromise between drugactivation andtissue penetration. Nevertheless, thepenetration of630nm light isstill poorandislikely tohavearange of5-10mm.Thisgives extra emphasis tothe development ofnewdrugswhichcanbeactivated bylight of700-800nm wavelengths. Considerable workistherefore being putintothedevelopment ofnewphotoactive drugs whichhaveequally goodas orbetter localising properties thanHPD,butcanbeactivated bylight oflonger wavelengths whichis morepenetrating intissue, thereby facilitating treatment oflarger tumourmasses. Thephthalocyanine
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