Twins in spirit part IV – [177Lu] high affinity DOTATATE

Brogsitter, Claudia; Hartmann, H.; Wunderlich, Gerd; Schottelius, Margret; Wester, Hans‐Jürgen; Kotzerke, Jörg

doi:10.3413/nukmed-0860-16-11

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…In addition, slower blood pool clearance could increase tracer bioavailability and thus renal DOTATATE retention ( 3 , 10 ). This hypothesis is based on the 68 Ga-DOTA-conjugated peptide kinetics with an early peak at about 5 min in the renal parenchymal and an early glomeruli washout as well as blood pool clearance in patients with unrestricted renal function ( 3 , 18 , 19 ). Of particular note, somatostatin receptors have been shown to have no significant effect on renal DOTATATE uptake ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans

Weissinger,

Seyfried,

Ursprung

et al. 2023

Front. Med.

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ObjectivePatients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT.MethodsIn total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK − EPI).ResultsSUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: −0.519, p < 0.001) and GFRCDK − EPI (r: −0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points.ConclusionThis pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed “Accumulation Index” (ACI).

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Section: Discussionmentioning

confidence: 99%

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans

Weissinger,

Seyfried,

Ursprung

et al. 2023

Front. Med.

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“…The high amount of peptide (20 µg/MBq) results in a maximum dose of 200 µg/10 MBq 225 Ac-labeled peptide, which is equal to the amount used for routine 177 Lu-preparations with 8000 MBq [ 33 ]. Typically, a single dose of 6–8 MBq is administered per patient, containing 120–160 µg peptide.…”

Section: Discussionmentioning

confidence: 99%

Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application

Pretze

Kunkel²,

Runge

et al. 2021

Pharmaceuticals

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The application of 225Ac (half-life T1/2 = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to 90Y, 177Lu or 188Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of 225Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies Eα = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with 177Lu or 90Y, can also accommodate 225Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of 225Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of 225Ac therapy. Independent which production pathway of 225Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the 225Ac-labeled peptides.

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“…As a first step toward population PK-informed predictions, actual differences in population PK parameters between both theranostic agents have to be determined (i.e., 68 Ga- and 177 Lu-labeled high-affinity DOTATATE (HA-DOTATATE) in our hospital [ 21 ]). Hence, the initial aim of this study was to assess population PK differences between [ 68 Ga]Ga-HA-DOTATATE and [ 177 Lu]Lu-HA-DOTATATE using a semi-physiological population PK modeling approach.…”

Section: Introductionmentioning

confidence: 99%

Predicting [177Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [68Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling

Siebinga,

de Wit-van der Veen,

Beijnen

et al. 2023

EJNMMI Phys

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Background Prediction 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. Methods A 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). Results Population 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. Conclusion Our 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.

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Twins in spirit part IV – [177Lu] high affinity DOTATATE

Cited by 9 publications

References 24 publications

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans

Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application

Predicting [177Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [68Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling

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