The role of patient-based treatment planning in peptide receptor radionuclide therapy

Hardiansyah, Deni; Maaß, Christian; Attarwala, Ali Asgar; Müller, Boris; Kletting, Peter; Mottaghy, Felix M.; Glatting, Gerhard

doi:10.1007/s00259-015-3248-6

Cited by 50 publications

(54 citation statements)

References 42 publications

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“…However, the extrapolation to smaller amounts led to considerably different results (Fig 4). In the light of the attempt of some working groups to use PET for pre-therapeutic dosimetry, extrapolation from measurements using small amounts of peptide to therapy with substantially higher amounts should be further investigated [44]. …”

Section: Discussionmentioning

confidence: 99%

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

et al. 2016

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In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.

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Section: Discussionmentioning

confidence: 99%

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

et al. 2016

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“…Tilted parallelograms represent inputs or outputs of a process while rectangles represent processes . First, an individualized patient PBPK model is developed and implemented to perform simulations of biokinetics using different molar amounts of peptide within a range of interest . From the simulations of biokinetics, time‐integrated activity coefficients (TIACs) and G factors (using repair rates μ rep and dose rates for the organs at risk (OARs) and tumor lesions) are calculated (Data ).…”

Section: Methodsmentioning

confidence: 99%

Treatment planning algorithm for peptide receptor radionuclide therapy considering multiple tumor lesions and organs at risk

et al. 2018

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“…In addition, it has to be considered that more sophisticated approaches exist, which can be used to predict the therapeutic biodistribution. For example, Hardiansyah et al recently presented a so-called physiologically based pharmacokinetic model that aims for individualization of treatment planned and integrates a variety of patient-specific data (e.g., weight, tumor volume, and glomerular filtration rate) (26).…”

Section: Discussionmentioning

confidence: 99%

Radiation Dosimetry for¹⁷⁷Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions

et al. 2016

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Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using 177 Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBEDCC)] ( 68 Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic 68 Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 6 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 6 0.21 Gy/GBq for the kidneys; 0.12 6 0.06 Gy/GBq for the liver; and 0.55 6 0.14 Gy/GBq for the parotid, 0.64 6 0.40 Gy/ GBq for the submandibular, and 3.8 6 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 6 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 6 2.9 Gy/GBq for the first, 3.3 6 2.5 Gy/GBq for the second, 2.7 6 2.3 Gy/GBq for the third, and 2.4 6 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r 5 0.44, P , 0.001 for SUV max ; r 5 0.43, P , 0.001 for SUV mean ) and moderately correlated with the change of SUV (r 5 0.478, P , 0.001 for SUV max , and r 5 0.50, P , 0.001 for SUV mean ). Conclusion: Organ-and tumorabsorbed doses for 177 Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of 177 Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection.

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The role of patient-based treatment planning in peptide receptor radionuclide therapy

Cited by 50 publications

References 42 publications

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

Treatment planning algorithm for peptide receptor radionuclide therapy considering multiple tumor lesions and organs at risk

Radiation Dosimetry for¹⁷⁷Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions

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The role of patient-based treatment planning in peptide receptor radionuclide therapy

Cited by 50 publications

References 42 publications

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

Treatment planning algorithm for peptide receptor radionuclide therapy considering multiple tumor lesions and organs at risk

Radiation Dosimetry for177Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions

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Radiation Dosimetry for¹⁷⁷Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions