REALTA’ REALTA’ E POTENZIALITA’ POTENZIALITA’ DEL NANOTECH IN LOMBARDIA 16 9414 +,11, 3(348,*3414.0, 3,156 ,7,38, , -9896 4 +,11( +0(.34780*( 5,6 02 2 (.030 * ?B7DE + EL;C 8H; Alessandro Maiocchi – Bracco Imaging SpA Centro Ricerche Bracco Outline % OZSf [e * ;: ?97B &C 7=?D= 8 % <a`fdSef 9YW`fe 7D: * ;: ?97B &C 7=?D= % * ;: ?97B LI * EB;9KB7HB_SY[`Y % F[UdabSdf[U^We I^SfXad_e Xad MKB % GS`abSdf[U^We b^SfXad_e Xad FJB % <a`U^ge[a`e What is medical Imaging ? Medical imaging refers to the techniques and processes used to create images of the human body (or parts thereof) for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and function). Electromagnetic Spectrum Examples of Medical Images and Devices % Radiograph Radiograph &DJ;DI?JOE<: ?7=DEIJ?9 P(dSke W A;2 7JJ;DK7J;: ?D 8E: O % Computed Tomography Tomography / F7J?7B V[efd[Tgf[a` E<4 . 7O SffW`gSf[a` UaWXX[U[W`fe ?D 8E: O Examples of Medical Images and Devices % Magnetic Resonance Imaging Imaging / F7J?7B V[efd[Tgf[a` E< bdafa` : ;DI?JO?D 8E: O % Ultrasound Ultrasound &DJ;DI?JOE<KBJH7IED?9 * % P I?=D7B dWX^WUfWV ?D 8E: O Examples of Medical Images and Devices % Nuclear Medicine Medicine &DJ;DI?JOE<"(dSke Xda_ 7 H7: ?EDK9B?: ; fdSUWd V[efd[TgfWV ?D 8E: O Positron Emission Tomography PET + emitters ( 15O, 13N, 11C, 18F) Single Photon Emission Computed Tomography SPECT emitters (99mTc, 123I, 111In) Medical Imaging in the World *XR ESCLUDE Barium & plain X-rays procedures AMR/Arlington Medical Resources, Inc., The Imaging Market Guide, 2006 1 BJH7IEKD: 4. 7O 0 7D: * . & 7H; J>; C EIJH;B;L7DJ * ;: ?97B &C 7=?D= FHE9;: KH;I ?D J>; >;7BJ> <79?B?J?;I The use of Contrast Agents in Medical Imaging % <a`fdSef SYW`fe 7H; KI;: ?D 9B?D?97B bdafaUa^e fa W`ZS`UW EH9H;7J; J>; D;9;II7HOL?IK7B 9EDJH7IJ?D 7D [_SYW TWfiWW` J>; EH=7D L;II;B EH JH79J?D M>?9> fZWk 7H; FH;I;DJ7D: J>; IKHHEKD: ?D= f[eegWe ?D J>; TaVk) % FS]W [f baee[T^W fa h[egS^[eW UWdfS[` S`Sfa_[US^ efdgUfgdWe EHF>OI?EBE=?97B Xg`Uf[a`e i[fZ[` J>; >KC 7D 8E: O M>;D J>; ?C 7=?D= fWUZ`[cgWe ED J>;?H ai` US``af bdah[VW fZ[e [`Xad_Sf[a` The Contrast Agents market P(JSk /+" 0>; ?C 7=?D= 7=;DJC 7HA;J ?IB;IIJ>7D 8?BB?ED E<J>; M>EB; F>7HC 79;KJ?97B C 7HA;J?D J>; MEHB: 8?BB?ED Current Contrast Agents: some examples PET MRI X-Ray SF 6 SPECT US Contrast Agents usage: some examples Contrast Agents usage: some examples 9`Y[aYdS_ Medical Imaging Research vs. Medical Needs * 7?D H;7I ED9EBE=O 97H: ?EL7I9KB7H7D: D;KHEBE=O % &DJ;=H7J;: IEBKJ?EDI78B; JE # &C FHEL; 799KH79OE<: ?7=DEI?I # $ K?: ; J>; 9EKHI; E<J>; JH;7JC ;DJ # 1 D: ;HIJ7D: J>; D7JKH; E<J>; : ?I;7I; ?D EH: ;HJE FH;: ?9J J>; H;IFED: ;HI JE 7 J>;H7FO* EB;9KB7H FWV[U[`W% -7J?;DJI #EBBEM KF # Strong focus on improvement of Patient Management Medical Imaging and Molecular Imaging What is Molecular Imaging? # 1 I;I?C 7=?D= J;9>DEBE=?;I JE 7II;II 8?EBE=?97B 79J?L?JO?D J>; 8E: O # &D L?LE 9>7H79J;H?P7J?ED E<7D: C ;7IKH;C ;DJE<8?EBE=?97B FHE9;II 7J9;BBKB7H7D: C EB;9KB7HB;L;B # - HE8; J>; C EB;9KB7H78DEHC 7B?J?;I7JJ>; 87I?IE<: ?I;7I; H7J>;HJ>7D ?C 7=?D= J>; ;D: ;<<;9JIE<J>; C EB;9KB7H 7BJ;H7J?EDI The practice of Medical Imaging in the era of Molecular Medicine Molecular imaging approaches Intracellular Accumulation Enzimatic activity Molecular targeting Metabolic activity Microtechnology and Ultrasound Imaging http://www.toshiba-europe.com/Medical/Materials/Visions: Magic Microbubbles 0*6 4)9))1,7 # /, ,+0*03, 4- 8/, 9896 , 0*6 4)9))1,7 84 +0(.347, *(3*,6 0*6 4)9))1,7 (3 2 (., 144+ % ,77,1 6 4: 8/ 3 # 92 46 7 2 (.03. # 92 46 3.04.,3,707 & 08/ 4386 (78$ 186(7493+ (3+ 0*6 4)9))1,7 (345(6 80*1,7 (3+ (7,67 6 ,(8, (3*,6 01103. 0*64)9))1,7 CNN’s live-show on Microbubbles and Ultrasound Contrast Agent Microtechnology and Ultrasound Imaging <a`fdSef ?D KBJH7IEKD: Sd[eWe Xda_ V[XXWdW`f Ua_bdWee[T[^[f[We E<J?IIK;I I 9EC FH;II?8?B?JO?D =7I;I [e adVWde E< C 7=D?JK: ; Z[YZWd fZS` fZSf E< <BK?: I J?IIK;I =7I<?BB;: _[UdaTgTT^We 7H; I;DI?J?L; KBJH7IEKD: 9EDJH7IJSYW`fe) )4 .; 8->--5 0< += ; >.= >; 0 *38<9385 4 94 /< (?/; 8938-4 . .3,4 7 # Microtechnology and Ultrasound Imaging 1 BJH7IEKD: &C 7=?D= $ 7IC ?9HE8K88B;I SonoVue™ kit K?1 IKBF>KH>;NSX^gad[VW &_ IZaebZa^[b[V K?1 IKBF>KH>;N7<BKEH?: ; >O: HEF>?B?9FEB; ZkVdabZaT[99>7?D Acoustic properties of soft-shell agents • Bubble oscillates linearly at extremely low acoustic pressures. • Bubble oscillates nonlinearly (higher harmonics) at slightly higher acoustic pressures. => basis for contrast agent specific detection techniques! Power spectrum of SonoVue™ + % ?=>IF;;: 97C ;H7 H;9EH: ?D= + : ; ' ED= W J affWdVS_%) - EM;H5: 6 (,+ fundamen tal 1 I;: <EH9EDJH7IJIF;9?<?9 : ;J;9J?ED J;9>D?GK;I (-+ 2n d harmonic (.+ (/+ (0+ (1+ + , - . / JH7DIC ?J<H;GK;D9O 0 1 2 3 #H;GK;D9O5* % P6 At high acoustic pressure, contrast agent microbubbles can be destroyed. expansion bubble in rest destruction disappearance compression % ?=>IF;;: 97C ;H7 H;9EH: ?D= ( #;HH7H7 1 fragments ! 7L?I Bubble destruction may be used for local perfusion quantification, by monitoring replenishment. Microtechnology and Ultrasound Imaging T= r02 . 2D .C b r ;gTT^W dSV[ge r r $ 7I: ;DI?JO r =[XXge[a` 9E;<< D r ED9 =7I ?D 8BEE: CT Atherosclerotic plaques (CEUS ) Detection of vunerable plaques of carotid ! ! - H;I;D9; : ; C ?9HE9?H9KB7J?ED ?DI?: ; J>; FB7GK;I C ?=>J?D: ?97J; J>; ?DIJ78?B?JOE<J>; FB7GK;I New microparticles platforms for Ultrasound O O Phospholipid (DPPE) O 2 O OH H N O O O Peptide Binder Lipid Membrane O O P SF6 Gas S HN P O A O C HN O E O R O O OH NH H N bWbf[VW O O N N O NH H N O COOH N H NH2 H2N TKPPR 2"$ #. . ;9;FJEHLSdYWf[`Y New microparticles platforms for Ultrasound / ?=D7B E8J7?D;: ?D JME : ?<<;H;DJ JKC EH C E: ;BI M?J> ( ! . J7H=;J;: "9>E &&&8K88B;I Echo III (Ctrl) Echo III-BRU2248 Rabbit (VX2) Rat (MatBIII) ,+++ 4++ 3++ JFK- 2++ 1++ 0++ /++ .++ Image obtained 25 min post-injection -++ ,++ + [ BA= [ BA= [ BA= New microparticles platforms for Ultrasound 1 BJH7IEKD: =K?: ;: fZda_Ta^ke[e L[eegW b^Se_[`aYW` SUf[hSfad ?J ?I 7 I;H?D; FHEJ;7I; J>7J97J7BOP;I J>; 9EDL;HI?ED E< b^Se_[`aYW` JE FB7IC ?D J>; C 7@ EH ;DPOC ; H;IFEDI?8B; <EH 9BEJ8H;7A: EMD Magnetic Resonance Imaging (MRI) Non-invasive and safe technique Great spatial resolution (mm scale) Outstanding diagnostic capability MR sagittal image of human head * . ?C 7=; dWbdWeW`fe 7 C 7FE<J>; ?DJ;DI?JOaX J>; % + * . I?=D7B E<M7J;HFHEJEDI 0>; 9EDJH7IJ[e _S[`^k YW`WdSfWV Tk V[XXWdW`UW ?D J>; H;B7N7J?ED f[_We 0 7D: 0 E< M7J;HFHEJEDI Alternative platforms for MRI CA Design Paramagnetic Metal Complexes Iron oxide nanoparticles Polychelating systems MRI Agents Gd-loaded nanotubes LipoCEST Superparamagnetic Particles for MRI + EHC 7BBO 9EKFB?D= XadUWe ?D XWdda_SY`Wf[U _SfWd[S^e 97KI; J>; C 7=D;J?9 _a_W`fe E< D;?=>8EH?D= Sfa_e fa 7B?=D dWeg^f[`Y ?D L;HO^SdYW [`fWd`S^ _SY`Wf[U X[W^V OZW` J>; J>;HC 7B W`WdYk [e egXX[U[W`f fa ahWdUa_W J>; Uagb^[`Y XadUWe J>; 7JEC ?9 _SY`Wf[U _a_W`fe 97D X^gUfgSfW dS`Va_^k 7D: J>; C 7J;H?7B ;N>?8?JI bSdS_SY`Wf[U TWZSh[ad) KgbWdbSdS_SY`Wf[e_ aUUgde iZW` J>; C 7J;H?7B Ua_baeWV E<L;HOe_S^^ UdkefS^^[fWe DC ?I Iron Oxides particles for MRI / - &, .;4<=59A " ! " ! ! " " ! $KgbWdbSdS_SY`Wf[U Bda` Hj[VWe% -<2>7;6 !45?>=2;$$$" #%!$" 1 / - &, 17;5=59A " ! " ! ! " " ! $M^fdSe_S^^ KgbWdbSdS_SY`Wf[U Bda` Hj[VWe% Iron Oxides particles for MRI Iron Oxides particles for MRI: some examples MRI image of liver metastasis before the adminitration of contrast agent Following infusion of Endorem®, ( Guerbert, UK), there is signal dropout in the normal liver, liver, with increased definition of the metastasis # 3 ) ) &/ # ' $ &) ". 0 R.Coll.Surg.Edinb 44 Iron Oxides particles for MRI: some examples ! ;J;9J?ED E<BOC F> `aVW _WfSefSeWe Detection mechanism Pre-contrast Post-contrast Self-assemlbled nanoparticles for MRI HfZWd `S`aefdgUfgdWV b^SfXad_e KD: ;H9KHH;DJWhS^gSf[a` KEG & 9_bZ[bZ[^[U @V(Ua_b^Wj 7 E[baea_W GS`aefdgUfgdWV @V(Ua`fS[`[`Y USdd[Wd F[UW^^We 07H=;JB?=7D: Self-assembled nanoparticles: paramagnetic SLN + ;M * . &9EDJH7IJ7=;DJI FB7J<EHC I 97D 8; : ;I?=D;: KI?D= / EB?: ) ?F?: + 7DEF7HJ?9B;I Imaging probe Solid Matrix: -OOC Ld[Y^kUWd[VWe IZaebZa^[b[Ve #7JJO 9?: I N N N N @V .& -OOC COOO C18H37 N C18H37 KfWS^fZ 9YW`f 07H=;J?D= E[YS`V ?; ! / -"- "$ ?; . $ ! Self-assemlbled nanoparticles: paramagnetic SLN Zeta potential B`fW`e[fk $]Ube% B`fW`e[fk $"% Size distribution 53 nm (35.5 mV $_N% =[S_WfWd $`_% 1 1 # " r1 ( )*+ c ,-. p T 1 T 1d * % P Z M7J;H ,*L : "C FJO/) + I(, d, /) + W $ : &&& C * e(, Tumor targeting: Animal model " 65=<A"& , L7H?7D 97H9?DEC 7 8;7H?D= 7B8 DKDK C EKI; C ?BB?ED 9;BBI IK89KJ7D;EKIBO?D@ ;9J;: ?D J>; X^S`] M;;AI SXfWd5 PR E 30 min post Tu mor Kidn eys " # ! # 2 7 % *2 ' 75(80(16,74198043 03 51(3, "N Tumor targeting: example of Folate-(p)SLNs results Pre 30 min post * EKI; 7 J?C ; 9EKHI; ID7FI>EJI 7<J;H #EB7J;BE7: ;: F+ -I [`\WUf[a` 4 h post 24 h post Tumor targeting: complete study results (p)NPs 0.05 mmol/kg Folate-(p)NPs 0.05 mmol/kg * p-value < 0.001 * p-value < 0.001 Conclusions Sensitivity "GK?FC ;DJI FEIJFHE9;II?D= C FB?<?97J?ED E<I?=D7BI % ?=>;HI?=D7BI <HEC I?D=B; FHE8;I % ?=> ;NJH7L7I7J?ED ?D J?IIK;I Specificity Safety - 7J>EBE=O * EB;9KB;I ?E9EC F7J?8B; C 7J;H?7BI % ?=> 7<<?D?JOC EB;9KB7HL;9JEHI / ;B<7II;C 8B;: IOIJ;C I ) EM . "/ KFJ7A; >jfdSUW^^gSd SYW`fe / >EHJ8BEE: B?<;J?C ; Thank you for your attention Rembrandt – Lezione di anatomia del professor Nicola Tulp - 1632