General Information of This Peptide-drug Conjugate (PDC)
PDC ID
PDC_00024
PDC Name
159Tb-PSMA-617
PDC Status
Investigative
Indication
In total 1 Indication(s)
Metastatic castration-resistant prostate cancer
Structure
Peptide Name
PSMA-617
 Peptide Info 
Receptor Name
Glutamate carboxypeptidase 2 (FOLH1)
 Receptor Info 
Drug Name
Terbium-159
 Drug Info 
Linker Name
(S)-2-(4-(aminomethyl)cyclohexane-1-carboxamido)-3-(naphthalen-2-yl)propanoic acid
 Linker Info 
Peptide Modified Type
The modification of binding with chemical molecules
Modified Segment
Urea
Formula
C49H68N9O16Tb
#Ro5 Violations (Lipinski): 5 Molecular Weight 1198.055347
Lipid-water partition coefficient (xlogp) -4.3821
Hydrogen Bond Donor Count (hbonddonor) 8
Hydrogen Bond Acceptor Count (hbondacc) 17
Rotatable Bond Count (rotbonds) 27
Full List of Activity Data of This Peptide-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 11 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell blocking rate < 0.50%
Administration Time 2 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

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Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

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In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell blocking rate < 0.50%
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

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In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell internalization rate
7.4 ± 0.4 %
Administration Time 2 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell internalization rate
9.9 ± 0.2 %
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell internalization rate
13 ± 1 %
Administration Time 2 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
The uptake of [175Lu]Lu-PSMA-617 in PC-3 PIP tumor cells determined by ICP-MS was 57 ± 5% (after 2 h) and 69 ± 6% (after 4 h), whereas it was 55 ± 2% (after 2 h) and 68 ± 5% (after 4 h) as determined by γ-counting for [177Lu]Lu-PSMA-617. For [159Tb]Tb-PSMA-617, the uptake in PC-3 PIP tumor cells determined by ICP-MS was 51 ± 4% (after 2 h) and 60 ± 5% (after 4 h), whereas for [161Tb]Tb-PSMA-617, it was 47 ± 3% (after 2 h) and 54 ± 6% (after 4 h) as determined by γ-counting.

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In Vitro Model Prostate carcinoma PSMA-positive PC-3 PIP cell CVCL_0035
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell internalization rate
17 ± 1 %
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
The uptake of [175Lu]Lu-PSMA-617 in PC-3 PIP tumor cells determined by ICP-MS was 57 ± 5% (after 2 h) and 69 ± 6% (after 4 h), whereas it was 55 ± 2% (after 2 h) and 68 ± 5% (after 4 h) as determined by γ-counting for [177Lu]Lu-PSMA-617. For [159Tb]Tb-PSMA-617, the uptake in PC-3 PIP tumor cells determined by ICP-MS was 51 ± 4% (after 2 h) and 60 ± 5% (after 4 h), whereas for [161Tb]Tb-PSMA-617, it was 47 ± 3% (after 2 h) and 54 ± 6% (after 4 h) as determined by γ-counting.

   Click to Show/Hide
In Vitro Model Prostate carcinoma PSMA-positive PC-3 PIP cell CVCL_0035
Experiment 7 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell uptake rate < 0.50%
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
The uptake of [175Lu]Lu-PSMA-617 in PC-3 PIP tumor cells determined by ICP-MS was 57 ± 5% (after 2 h) and 69 ± 6% (after 4 h), whereas it was 55 ± 2% (after 2 h) and 68 ± 5% (after 4 h) as determined by γ-counting for [177Lu]Lu-PSMA-617. For [159Tb]Tb-PSMA-617, the uptake in PC-3 PIP tumor cells determined by ICP-MS was 51 ± 4% (after 2 h) and 60 ± 5% (after 4 h), whereas for [161Tb]Tb-PSMA-617, it was 47 ± 3% (after 2 h) and 54 ± 6% (after 4 h) as determined by γ-counting.

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In Vitro Model Prostate carcinoma PSMA-negative PC-3 flu cell CVCL_0035
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell uptake rate
12 ± 1 %
Administration Time 2 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 9 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell uptake rate
13 ± 1 %
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
In LNCaP cells, the uptake of [175Lu]Lu-PSMA-617 determined by ICP-MS was 13 ± 2% (after 2 h) and 18 ± 2% (after 4 h). γ-Counting revealed the uptake of [177Lu]Lu-PSMA-617 in LNCaP cells of 11 ± 1% (after 2 h) and 14 ± 1% (after 4 h). For [159Tb]Tb-PSMA-617, analysis by ICP-MS revealed the uptake in LNCaP cells of 12 ± 1% (after 2 h) and 13 ± 1% (after 4 h). For the radioligand [161Tb]Tb-PSMA-617, the uptake in LNCaP cells determined by γ-counting was 7.8 ± 0.8% (after 2 h) and 9.7 ± 0.2% (after 4 h).

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 10 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell uptake rate
51 ± 4 %
Administration Time 2 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

   Click to Show/Hide
Description
The uptake of [175Lu]Lu-PSMA-617 in PC-3 PIP tumor cells determined by ICP-MS was 57 ± 5% (after 2 h) and 69 ± 6% (after 4 h), whereas it was 55 ± 2% (after 2 h) and 68 ± 5% (after 4 h) as determined by γ-counting for [177Lu]Lu-PSMA-617. For [159Tb]Tb-PSMA-617, the uptake in PC-3 PIP tumor cells determined by ICP-MS was 51 ± 4% (after 2 h) and 60 ± 5% (after 4 h), whereas for [161Tb]Tb-PSMA-617, it was 47 ± 3% (after 2 h) and 54 ± 6% (after 4 h) as determined by γ-counting.

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In Vitro Model Prostate carcinoma PSMA-positive PC-3 PIP cell CVCL_0035
Experiment 11 Reporting the Activity Data of This PDC [1]
Indication Metastatic castration-resistant prostate cancer
Efficacy Data Cell uptake rate
60 ± 5 %
Administration Time 4 h
Administration Dosage 0.75 nM
Evaluation Method ICP-MS or γ-counting assay
MOA of PDC
This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a proof-of-concept study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

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Description
The uptake of [175Lu]Lu-PSMA-617 in PC-3 PIP tumor cells determined by ICP-MS was 57 ± 5% (after 2 h) and 69 ± 6% (after 4 h), whereas it was 55 ± 2% (after 2 h) and 68 ± 5% (after 4 h) as determined by γ-counting for [177Lu]Lu-PSMA-617. For [159Tb]Tb-PSMA-617, the uptake in PC-3 PIP tumor cells determined by ICP-MS was 51 ± 4% (after 2 h) and 60 ± 5% (after 4 h), whereas for [161Tb]Tb-PSMA-617, it was 47 ± 3% (after 2 h) and 54 ± 6% (after 4 h) as determined by γ-counting.

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In Vitro Model Prostate carcinoma PSMA-positive PC-3 PIP cell CVCL_0035
References
Ref 1 Inductively Coupled Plasma Mass SpectrometryA Valid Method for the Characterization of Metal Conjugates in View of the Development of Radiopharmaceuticals. Mol Pharm. 2023 Apr 3;20(4):2150-2158. doi: 10.1021/acs.molpharmaceut.2c01092. Epub 2023 Feb 24.