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Despite the importance of the glucagon receptor (GCGR) in disease and in pharmaceutical drug development, there is a lack of specific and sensitive biomarkers of its activation in humans. The PET radioligand Ga-68-DO3A-VS-Tuna-2 (Ga-68-Tuna-2) was developed to yield a noninvasive imaging marker for GCGR target distribution and drug target engagement in humans. Methods: The biodistribution and dosimetry of Ga-68-Tuna-2 was assessed by PET/CT in 13 individuals with type 2 diabetes as part of a clinical study assessing the occupancy of the dual GCGR/glucagon like peptide-1 receptor agonist SAR425899. Binding of Ga-68-Tuna-2 in liver and reference tissues was evaluated and correlated to biometrics (e.g., weight or body mass index) or other biomarkers (e.g., plasma glucagon levels). Results: Ga-68-Tuna-2 binding was seen primarily in the liver, which is in line with the strong expression of GCGR on hepatocytes. The kidneys demonstrated high excretion-related retention, whereas all other tissue demonstrated rapid washout. The SUV55 (min) (SUV during the last 10-min time frame, 50-60 min after administration) uptake endpoint was sensitive to endogenous levels of glucagon. Ga-68-Tuna-2 exhibited a safe dosimetry profile and no adverse events after intravenous administration. Conclusion: Ga-68-Tuna-2 can be used for safe and accurate assessment of the GCGR in human. It may serve as an important tool in understanding the in vivo pharmacology of novel drugs engaging the GCGR.

Introduction: [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 (previously published as [Ga-68]Ga-DO3A-VS-Cys(40)-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements.Methods:The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for(68)Ga-labeling, and pharmaceutical-grade(68)Ge/Ga-68 generator (GalliaPharm(R)) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys(40)-Tuna-2 (GMP-grade) was provided by Sanofi Aventis.Results:The reproducible and GMP-compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 +/- 2.5% (n= 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 +/- 0.6% (n= 17) with the total amount of the peptide in the preparation of 48 +/- 2 mu g (n= 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h.Conclusion:The fully automated GMP-compliant manufa

Introduction: [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 (previously published as [Ga-68]Ga-DO3A-VS-Cys(40)-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements.Methods:The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for(68)Ga-labeling, and pharmaceutical-grade(68)Ge/Ga-68 generator (GalliaPharm(R)) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys(40)-Tuna-2 (GMP-grade) was provided by Sanofi Aventis.Results:The reproducible and GMP-compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 +/- 2.5% (n= 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 +/- 0.6% (n= 17) with the total amount of the peptide in the preparation of 48 +/- 2 mu g (n= 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h.Conclusion:The fully automated GMP-compliant manufa

Introduction: [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 (previously published as [Ga-68]Ga-DO3A-VS-Cys(40)-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements.Methods:The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for(68)Ga-labeling, and pharmaceutical-grade(68)Ge/Ga-68 generator (GalliaPharm(R)) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys(40)-Tuna-2 (GMP-grade) was provided by Sanofi Aventis.Results:The reproducible and GMP-compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 +/- 2.5% (n= 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 +/- 0.6% (n= 17) with the total amount of the peptide in the preparation of 48 +/- 2 mu g (n= 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h.Conclusion:The fully automated GMP-compliant manufa

Introduction: [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 (previously published as [Ga-68]Ga-DO3A-VS-Cys(40)-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements.Methods:The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for(68)Ga-labeling, and pharmaceutical-grade(68)Ge/Ga-68 generator (GalliaPharm(R)) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys(40)-Tuna-2 (GMP-grade) was provided by Sanofi Aventis.Results:The reproducible and GMP-compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 +/- 2.5% (n= 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 +/- 0.6% (n= 17) with the total amount of the peptide in the preparation of 48 +/- 2 mu g (n= 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h.Conclusion:The fully automated GMP-compliant manufa

Introduction: [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 (previously published as [Ga-68]Ga-DO3A-VS-Cys(40)-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements.Methods:The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for(68)Ga-labeling, and pharmaceutical-grade(68)Ge/Ga-68 generator (GalliaPharm(R)) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys(40)-Tuna-2 (GMP-grade) was provided by Sanofi Aventis.Results:The reproducible and GMP-compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 +/- 2.5% (n= 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 +/- 0.6% (n= 17) with the total amount of the peptide in the preparation of 48 +/- 2 mu g (n= 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h.Conclusion:The fully automated GMP-compliant manufa