Positron emission tomography (PET) ntsuas qhov twg cov tshuaj radiolabeled, biologic, nanoparticle, lossis cell therapy mus rau hauv lub cev muaj sia. Hauv kev tshawb fawb tsis yog -tib neeg primate (NHP), nws qhov txiaj ntsig tseem ceeb yog teb cov lus nug uas qhov kev txiav txim siab tsis tuaj yeem: tsis yog tias tus neeg sib tw mus txog nws lub hom phiaj, tab sis nws mus qhov twg, nws kis mus deb npaum li cas los ntawm qhov chaw txhaj tshuaj, thiab tus qauv ntawd hloov mus li cas.
Cov lus nug no tseem ceeb tshaj plaws rau cov tshuaj tiv thaiv thiab kev kho nanoparticle, qhov twg txoj hauv kev los ntawm cov qog ntshav qab zib feem ntau txiav txim siab ntau npaum li cas antigen mus txog cov dej ntws thiab, dhau los, qhov kev tiv thaiv kab mob muaj zog npaum li cas.
A 2021 ntawv hauvBiomaterialsqhia tias qhov no zoo li cas hauv kev xyaum. Martin thiab cov npoj yaig tau taug qab cov tshuaj tiv thaiv nanoparticle hauv rhesus macaques nrog PET ntxiv rau cov ntaub so ntswg - qib fluorescence imaging, ua hauj lwm los ntawm tag nrho cov tsiaj mus rau ib tug neeg follicles. Tom qab txhaj tshuaj tiv thaiv tus ncej puab, cov teeb liab tshuaj tiv thaiv tau tshwm sim hauv cov qog nqaij hlav inguinal thiab iliac, qee qhov deb li 17 cm ntawm qhov chaw txhaj tshuaj. Ntawm cov ntaub so ntswg, nanoparticle-pom cov hnab ntawv HIV antigen tau sib sau ua ke ntawm follicular dendritic cell (FDC) tes hauj lwm hauv B- cell follicles.
Kev noj tshuaj rau cov neeg tsim tshuaj: kev kos duab tso cai rau koj txuas qhov tshwm sim ntawm qhov chaw txhaj tshuaj mus rau qhov twg cov khoom xaus, tsis tas yuav tua tsiaj txhua lub sijhawm kom paub.
PET Ntxiv rau Biodistribution Studies yog dab tsi?
Biodistribution ua hauj lwm yeej ib txwm txhais tau tias tua tsiaj thaum lub sij hawm cov ntsiab lus thiab ces ntsuas cov ntaub so ntswg: gamma suav, autoradiography, histology, los yog ib co bioanalytical nyeem ntawv. Txhua lub sijhawm taw tes yog tsiaj sib txawv, yog li koj tsuas yog tau txais ib qho snapshot.
PET tshem tawm qhov kev txwv ntawd. Koj tuaj yeem ua duab tib yam tsiaj ntau zaus thiab saib cov ntawv xov tooj cua txav.
Hauv kev ua haujlwm preclinical no ib leeg muaj peev xwm nchuav rau hauv ob peb nqe lus nug ib zaug: qhov twg cov khoom mus, nws ceev npaum li cas, seb nws mus txog lub hom phiaj, thiab seb qhov kev faib khoom puas haum rau cov txheej txheem tau hais tseg. Rau cov kev tshawb fawb NHP tshwj xeeb, qhov sib piv nrog cov ntaub so ntswg ua haujlwm zoo li no:
| Mus kom ze | Cov ntaub ntawv tseem ceeb | Cov yam ntxwv tseem ceeb |
|---|---|---|
| PET duab | Tag nrho -lub cev thiab cheeb tsam biodistribution | Longitudinal, tsis yog -invasive |
| Ex vivo cov ntaub so ntswg tsom xam | Cov ntaub so ntswg concentration thiab molecular muaj pes tsawg leeg | Terminal, quantitative |
| Histology / immunohistochemistry | Cov ntaub so ntswg thiab cellular localization | High spatial daws teeb meem |
| Fluorescence duab | Cov ntaub so ntswg- theem faib | High spatial daws teeb meem, feem ntau ex vivo |
| MRI / CT | Anatomy thiab structural ntsiab lus | High anatomical daws teeb meem |
PET tsis yog ib qho sawv ntsug - rau kev tshuaj xyuas cov ntaub so ntswg. Nws tus nqi tshwm sim thaum koj ua ke tag nrho - lub cev molecular duab nrog lub cev thiab cov ntaub so ntswg - theem kawg.
Kev Tshawb Fawb Rhesus Macaque ntawm Lymphatic -Targeting Vaccines
Martin cov pab pawg tau tsim cov tshuaj tiv thaiv subunit txhais tau tias yuav caij cov qog ntshav: ib lub hnab ntawv HIV trimer mounted rau ntawm nanoparticle (trimer-NP), ua ke nrog cov lipid-conjugated CpG adjuvant (amph{2}}CpG). Lawv siv PET ua ke nrog cov ntaub so ntswg fluorescence imaging los txuas tag nrho -tsiaj duab rau dab tsi tshwm sim nyob rau hauv ib tug neeg nodes.
Tom qab kev txhaj tshuaj ntawm tus ncej puab, PET khaws cov tshuaj tiv thaiv feem ntau nyob rau hauv inguinal thiab iliac nodes. Teeb liab mus txog iliac nodes 17 cm ntawm qhov chaw txhaj tshuaj.
Qhov kev ncua deb ntawd tseem ceeb. Nws qhia tau hais tias koj tsis tuaj yeem xav tias cov kua dej tso tawm ntawm qhov chaw ze tshaj plaws. Hauv cov tsiaj loj, tus neeg taug qab hla anatomically cais cov lymphatic chaw nres tsheb uas tus qauv hauv zos yuav nco. NHP PET khwv tau nws qhov chaw hauv cov tshuaj tiv thaiv ua haujlwm ntawm no: nws qhia txog qhov tseeb ntawm lymphatic kis nyob rau hauv cov tsiaj nyob, es tsis txhob ntawm cov nodes ib tus neeg txiav txim siab sau ua ntej.
Los ntawm tag nrho -Lub cev Biodistribution mus rau Lymph Node Microanatomy
Kev sib koom ua ke ntawm PET nrog cov duab kos duab yog qhov kev tshawb fawb no tau nthuav dav.PET teeb tsa tus qauv macro: inguinal thiab iliac nodes ua qhov chaw txhawb nqa loj. Fluorescence imaging tom qab ntawd pom tias cov tshuaj tiv thaiv kab mob nyob hauv cov nodes li cas. Cov nanoparticle-pom cov duab trimer tau sau nyob ib ncig ntawm cov npoo ntawm FDC tes hauj lwm hauv B-cov follicles. Qhov chaw ntawd ua rau muaj kev nkag siab zoo txog kev lom neeg: FDCs yog qhov scaffold ntawm lymphoid follicle thiab cov qauv uas tuav cov antigen hauv cov kab mob hauv nruab nrab.
Tab sis cov duab tsis ua pov thawj ua rau. Txoj kev tshawb no pom cov antigen zaum ntawm FDC tes hauj lwm; nws tsis tau qhia, los ntawm PET ib leeg, tias qhov kev teeb tsa no tsim tau zoo dua B-cell tiv thaiv kab mob. Kev kos duab qhia koj tias cov khoom nyob qhov twg. Txawm hais tias qhov chaw ntawd ua rau lub cev tiv thaiv kab mob yog ib lo lus nug cais, thiab koj xav tau kev nyeem ntawv tiv thaiv kab mob los teb nws.
Lub workflow chains ua ke zoo li no:
PET → regional faib → cov ntaub so ntswg imaging → cellular qhov chaw → tiv thaiv kab mob los yog pharmacodynamic tshwm sim
Txhua kauj ruam ntxiv qhov yav dhau los tsis tuaj yeem pom ntawm nws tus kheej.
Vim li cas 17 cm Nrhiav Teeb Meem rau NHP Biodistribution Research
Daim duab 17 cm yog tus naj npawb uas txhua tus nco tau los ntawm daim ntawv no, tab sis nws tsuas yog txhais tau tias qee yam hauv cov ntsiab lus.
Cov txiaj ntsig tau los ntawm ib qho tshuaj tiv thaiv kab mob HIV, muab rau hauv ib qhov chaw, hauv rhesus macaques. Nws tsis yog ib txoj cai rau yuav ua li cas txhaj tshuaj tiv thaiv, thiab koj yuav tsum tsis txhob kho 17 cm raws li ib tug ruaj anatomical nrug uas tuav thoob plaws NHP kev tshawb fawb. Qhov nws qhia tau hais tias qhov kev cuam tshuam ntawm lymphatic nyob deb tuaj yeem loj, thiab PET tuaj yeem ntsuas nws.
Rau ib tus neeg tsim cov tshuaj tiv thaiv, nanoparticle, lossis tshuaj tiv thaiv kab mob uas taug kev los ntawm cov qog ntshav, qhov kev tshawb nrhiav tsa ib pawg ntawm cov lus nug: qhov twg cov khoom siv tom qab txhaj tshuaj, cov nodes pom qhov twg, cov qauv puas hloov pauv tus qauv, thiab puas muaj kab mob tiv thaiv kab mob lossis cov tshuaj pharmacodynamic uas koj xav tau? PET teb thawj ob peb yam. Cov ntaub so ntswg thiab kev tiv thaiv kab mob yuav tsum kaw lub voj ntawm tus so.
PET yog Biodistribution Tool, tsis yog ib qho kev soj ntsuam kev ua tau zoo
PET teeb liab tsis yog tib yam li kev ua si. Lub koob yees duab pom cov radionuclide, nyob qhov twg nws mus: cov tshuaj tsis zoo, cov tshuaj metabolite, cov khoom tawg, lossis lwm yam tseem nqa daim ntawv lo. Qhov twg koj tab tom saib nyob ntawm seb koj sau nws li cas.
Yog li kev tshawb fawb PET biodistribution xav tau lub tuam txhab. Ib qho tshuaj tiv thaiv lossis nanoparticle program feem ntau sau nws nrog rau kev kuaj ntshav rau PK lub cev, cov qauv kuaj rau cov ntaub so ntswg, ntws cytometry rau kev tiv thaiv kab mob-cell profileing, immunohistochemistry rau qhov chaw, thiab cov kev ntsuam xyuas ua haujlwm rau kev nyeem cov tshuaj pharmacodynamic. Qhov no tseem ceeb tshaj plaws rau biologics thiab nanoparticles, qhov twg cov tracer thiab cov khoom siv tsis tas yuav nyob nrog.
Xaiv PET Radionuclide rau NHP Biodistribution Studies
Xaiv cov radionuclide kom phim ntev npaum li cas cov ntawv teev npe molecule nyob ib puag ncig thiab nws txav mus li cas.
Cov uas nquag,18F, 68 ua g, 64 ua, 8 9 tzr, thiab124I, npog ntau yam ntawm lub cev ib nrab -lub neej.18Fdecays nyob rau hauv li 110 feeb,64 uanyob rau hauv kwv yees li 12.7 teev,8 9 tzrhauv kwv yees li 3.27 hnub. Ceev- txav me me molecules haum lub luv- nyob isotopes; cov tshuaj tiv thaiv kab mob, nanoparticles, thiab lwm yam biologics qeeb xav tau ntev - cov neeg nyob zoo li8 9 tzrkom nyob twj ywm imageable hla lub qhov rais koj mob siab txog.
Labeling kuj yuav tsum tau tawm ntawm lub molecule nws tus kheej kom zoo. Hloov nws qhov loj me, them nqi, lipophilicity, khi, lossis ruaj khov thiab koj tuaj yeem hloov qhov nws mus. Kho radiolabeling raws li kev kawm tsim, tsis yog lub thawv rau zuam ua ntej scan.
Vim li cas thiaj siv Tsis yog -Human Primates rau Molecular Imaging?
NHPs zaum ntawm nas thiab chaw kho mob. Lawv loj txaus los luam theej duab ntawm tib lub tshuab thiab cov txheej txheem siv hauv tib neeg, thiab lawv lub cev yog ze rau peb li nas.
Prisys 'Biodistribution Imaging Service platformua haujlwm kho mob- sib npaug MRI, CT, PET-CT, thiab DSA, teeb tsa rau kev ntsuas rov ua dua ntawm tus kab mob, kev faib tshuaj, kev ua tau zoo, thiab biomarkers. Raumolecular duab, qhov them nyiaj tau tuaj yeem nyeem PET tiv thaiv lub cev: PET / CT kab teeb liab nrog cov qauv, thiab MRI ntxiv cov mos-cov ntaub so ntswg nthuav dav. Lub ntsiab lus ntawm NHP duab tsis yog PET scan ntawm nws tus kheej. Nws tau koom nrog cov duab ntawd rau kev kho tshuaj, bioanalysis, pathology, thiab tus qauv kab mob.
Integrating PET Imaging rau NHP Drug Development
Kev kawm zoo NHP PET pib los ntawm cov lus nug, tsis yog los ntawm "cia peb tau txais cov duab biodistribution."
Rau cov tshuaj tiv thaiv lossis nanoparticle, kev ua haujlwm feem ntau ua haujlwm: daim ntawv lo thiab QC cov khoom, siv lub hauv paus scan yog tias xav tau, ua haujlwm, tom qab ntawd tau txais serial PET / CT, kos cov cheeb tsam txaus siab, thiab thaum kawg khi cov lej rau cov ntshav, cov ntaub so ntswg, thiab cov ntaub ntawv pharmacodynamic. Cov ntaub ntawv qhia rau koj seb tus neeg sib tw tau mus txog qhov chaw nws tau txhais li cas rau, thiab qhov raug hloov pauv li cas thaum lub sijhawm.
Kev kos duab rub nws qhov hnyav thoob plaws tag nrho cov kev pab cuam preclinical: kev faib tawm, PK, lub hom phiaj kev koom tes, PD, kev ua tau zoo, biomarkers. Nyob rau hauv NHPs ntug yog longitudinal: koj ua raws ib tug tsiaj los ntawm txhua lub sij hawm taw tes es tsis txhob hlawv ib tug tshiab cohort rau txhua scan. Terminal cov ntaub so ntswg ua hauj lwm tseem khwv tau nws qhov chaw thaum koj xav tau molecular lossis cellular daws teeb meem lub koob yees duab tsis tuaj yeem muab rau koj.
Los ntawm Biodistribution mus rau Translational Decision-Ua
Kev nyeem cov ntaub ntawv PET zoo txhais tau tias ntau dua li daim ntawv qhia qhov twg cov tshuaj mus. Cov lus nug tiag tiag yog seb tus qauv puas phim lub tshuab koj tsim rau.
Siv cov tshuaj tiv thaiv uas tsim los txhawm rau txhawm rau cov qog ntshav qab zib. PET paub meej tias cov nodes tau raug nthuav tawm. Cov ntaub so ntswg imaging qhia qhov twg cov antigen zaum hauv lawv. Cov tshuaj tiv thaiv kab mob hais tias seb qhov chaw ntawd tuaj nrog B-cell, T- cell, lossis cov tshuaj tiv thaiv kab mob uas koj xav tau. Chain khiav:
Kev tswj hwm → kev faib tawm → phiaj xwm - cov ntaub so ntswg raug → cellular qhov chaw → pharmacodynamic teb → qhov tshwm sim
Txhaum nws nyob qhov twg thiab zaj dab neeg poob sib nrug. Tus neeg sib tw tuaj yeem ncav cuag cov ntaub so ntswg zoo yam tsis tau koom nrog lub hom phiaj, lossis pawg hauv cov ntaub so ntswg yam tsis ua dab tsi pab tau. PET yog ib qho txuas hauv cov saw hlau, muaj zog tsuas yog thaum lub chaw muag tshuaj thiab cov ntaub so ntswg ua haujlwm txuas rau nws.
Xaus
PET muab txoj hauv kev rau koj los saib cov tshuaj txav mus los ntawm qhov tsis yog - tib neeg primate nyob rau lub sijhawm, muaj txiaj ntsig zoo tshaj plaws thaum qhov kev faib tawm nyuaj dhau ntawm qhov chaw lossis sijhawm rau cov ntaub so ntswg los ntawm lub davhlau ya nyob twg los ntes.
Martin txoj kev tshawb fawb rhesus yog ib qho piv txwv huv: PET pom cov tshuaj tiv thaiv nyob rau hauv inguinal thiab iliac nodes, tawm mus rau 17 cm ntawm tus ncej puab, thiab cov ntaub so ntswg fluorescence tso cov nanoparticle antigen nyob ib ncig ntawm FDC tes hauj lwm nyob rau hauv lub follicles.
Zaj lus qhia rau cov neeg tsim khoom yog nyeem biodistribution ua ib feem ntawm cov ntaub ntawv txhais lus tag nrho, tsis yog ib qho duab sawv cev. PET muab qhov longitudinal tag nrho- lub cev saib; CT lossis MRI muab lub cev; cov ntaub so ntswg imaging daws cov ntsiab lus hauv zos; PK/PD, kev tiv thaiv kab mob, thiab kev ua haujlwm pathology txiav txim siab tias nws txhais li cas. Rau cov tshuaj tiv thaiv, nanoparticles, biologics, thiab kev kho ntawm tes, qhov sib xyaw ua ke yog qhov qhia koj tias tus neeg sib tw ua li cas ua ntej nws mus txog qhov chaw kho mob.
Pom zoo nyeem
Molecular Imaging Biomarkers: Txhim Kho Kev Tshawb Fawb Kev Txhais Lus Thiab Kev Txhim Kho Tshuaj
Vim li cas NHP Molecular Imaging yog qhov tseem ceeb rau Kev Txhais Lus PET Studies
Dab tsi yog Molecular Imaging thiab Vim Li Cas Nws Tseem Ceeb Hauv Kev Txhim Kho Tshuaj?
NHP Radionuclide Biodistribution Studies: Molecular Imaging For Translational Drug Development
Cov ntaub ntawv
Martin JT, Hartwell BL, Kumarapperuma SC, et al. Ua ke PET thiab tag nrho - daim duab duab ntawm lymphatic - tsom rau cov tshuaj tiv thaiv hauv tsis yog - tib neeg primates.Biomaterials. 2021; 275:120868. doi: 10.1016/j.biomaterials.2021.120868.
FAQ
Q: Dab tsi yog PET biodistribution imaging hauv NHP kev tshawb fawb?
A: Koj sau cov tshuaj, biologic, nanoparticle, lossis lwm yam khoom siv kuaj nrog cov positron emitter, tom qab ntawd saib thiab ntsuas qhov twg nws mus rau hauv cov tsiaj nyob hauv lub sijhawm. Nws npog tag nrho - lub cev thiab cheeb tsam kev faib tawm, thiab nws ua haujlwm nrog rau cov ntaub so ntswg soj ntsuam es tsis hloov nws.
Q: Vim li cas thiaj siv PET imaging es tsis txhob sau cov ntaub so ntswg?
A: Kev sau cov ntaub so ntswg ntsuas cov khoom siv tiag tiag, tab sis txhua lub sijhawm xav tau cov tsiaj sib txawv, yog li koj tsuas yog tau txais cov duab thaij duab. PET cov duab tib yam tsiaj ib zaug ntxiv, muab sijhawm rau koj los ntawm kev siv cov qauv sib txuas.
Q: Kev tshawb fawb tshuaj tiv thaiv rhesus macaque tau ua dab tsi?
A: Tom qab txhaj koob tshuaj tiv thaiv tus ncej puab, lymphatic - cov tshuaj tiv thaiv kab mob tau tshwm sim feem ntau hauv cov kab mob inguinal thiab iliac, nrog cov teeb liab ncav cuag iliac nodes 17 cm tawm. Cov duab kos duab tso cov nanoparticle antigen nyob ib ncig ntawm FDC tes hauj lwm hauv B-cov follicles.
Q: Puas yog PET daim duab qhia pom kev sib koom tes lossis kev ua tau zoo?
A: Tsis yog nws tus kheej. PET qhia tias daim ntawv lo mus qhov twg. Lub hom phiaj kev koom tes thiab kev ua tau zoo xav tau cov molecular, cellular, functional, lossis pathological readouts los txhawb lawv.
Q: Dab tsi radionuclides tuaj yeem siv rau kev tshawb fawb PET biodistribution?
A: Cov txheej txheem ib txwm yog18F, 68 ua g, 64 ua, 8 9 tzr, thiab124I. Xaiv raws li tus neeg sib tw clears, ntev npaum li cas koj yuav tsum tau duab, thiab dab tsi lub labeling chemistry thiab tracer stability tso cai.
Q: PET puas tuaj yeem ua ke nrog lwm yam kev ntsuas hauv kev tshawb fawb NHP?
A: Yog. PET nrog CT lossis MRI ntxiv lub cev; cov ntaub so ntswg fluorescence, histology, los yog immunohistochemistry sau nyob rau hauv lub zos thiab cellular nthuav dav. Prisys 'NHP platform muaj PET-CT, MRI, CT, thiab DSA rau hom kev txhais lus no.
