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Predicting [177Lu]L...
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Siebinga, HinkeNetherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.;Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.;Univ Utrecht, Grad Sch Life Sci, Utrecht, Netherlands.
(författare)
Predicting [177Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [68Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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Springer,2023
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-520032
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-520032URI
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https://doi.org/10.1186/s40658-023-00565-4DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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BackgroundPrediction of [177Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [68Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [177Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [177Lu]Lu-HA-DOTATATE and [68Ga]Ga-HA-DOTATATE were assessed and subsequently [177Lu]Lu-HA-DOTATATE was predicted based on [68Ga]Ga-HA-DOTATATE imaging.MethodsA semi-physiological nonlinear mixed-effects model was developed for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment). Model parameters were fixed based on a previously developed physiologically based pharmacokinetic model for [68Ga]Ga-HA-DOTATATE. For [177Lu]Lu-HA-DOTATATE, PK parameters were based on literature values or estimated based on scan data (four time points post-injection) from nine patients. Finally, individual [177Lu]Lu-HA-DOTATATE uptake into tumors and kidneys was predicted based on individual [68Ga]Ga-HA-DOTATATE scan data using Bayesian estimates. Predictions were evaluated compared to observed data using a relative prediction error (RPE) for both area under the curve (AUC) and absorbed dose. Lastly, to assess the predictive value of diagnostic imaging to predict therapeutic exposure, individual prediction RPEs (using Bayesian estimation) were compared to those from population predictions (using the population model).ResultsPopulation uptake rate parameters for spleen, kidney and tumors differed by a 0.29-fold (15% relative standard error (RSE)), 0.49-fold (15% RSE) and 1.43-fold (14% RSE), respectively, for [177Lu]Lu-HA-DOTATATE compared to [68Ga]Ga-HA-DOTATATE. Model predictions adequately described observed data in kidney and tumors for both peptides (based on visual inspection of goodness-of-fit plots). Individual predictions of tumor uptake were better (RPE AUC –40 to 28%) compared to kidney predictions (RPE AUC –53 to 41%). Absorbed dose predictions were less predictive for both tumor and kidneys (RPE tumor and kidney –51 to 44% and –58 to 82%, respectively). For most patients, [177Lu]Lu-HA-DOTATATE tumor accumulation predictions based on individual PK parameters estimated from diagnostic imaging outperformed predictions based on population parameters.ConclusionOur semi-physiological PK model indicated clear differences in PK parameters for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE. Diagnostic images provided additional information to individually predict [177Lu]Lu-HA-DOTATATE tumor uptake compared to using a population approach. In addition, individual predictions indicated that many aspects, apart from PK differences, play a part in predicting [177Lu]Lu-HA-DOTATATE distribution.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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de van der Veen, Berlinda J.Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.
(författare)
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Beijnen, Jos H.Netherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
(författare)
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Stokkel, Marcel P. M.Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.
(författare)
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Dorlo, Thomas P. C.,PhD,1983-Uppsala universitet,Institutionen för farmaci,Netherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands(Swepub:uu)thodo249
(författare)
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Huitema, Alwin D. R.Netherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.;Univ Utrecht, Univ Med Ctr Utrecht, Dept Clin Pharm, Utrecht, Netherlands.;Princess Maxima Ctr Pediat Oncol, Dept Pharmacol, Utrecht, Netherlands.
(författare)
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Hendrikx, Jeroen J. M. A.Netherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.;Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.
(författare)
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Netherlands Canc Inst, Dept Pharm & Pharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.;Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.;Univ Utrecht, Grad Sch Life Sci, Utrecht, Netherlands.Netherlands Canc Inst, Dept Nucl Med, Amsterdam, Netherlands.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:EJNMMI Physics: Springer10:12197-7364
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