p-SCN-Macropa is a bifunctional macrocyclic chelator featuring macrocyclic polyamine skeletons and thiocyanate (-SCN) reactive moieties. p-SCN-Macropa can conjugate with monoclonal antibodies including Nimotuzumab, Rituximab and Trastuzumab -PEG6-DM1 for 225 Ac radiolabeling to construct radioimmunoconjugates. p-SCN-Macropa is applicable for the research of colorectal cancer, HER2-positive breast cancer, TROP-2-positive cancers, and PSMA-positive cancers [1] [2] [3].
In Vivo, p-SCN-Macropa-containing radioimmunoconjugate [225Ac]Ac-macropa-Nimotuzumab (13 kBq per dose; i.v.; on days 0, 10, and 20) achieved complete tumor regression in 43% of KRASG12C-mutant DLD-1 and 14% of BRAFV600E-mutant HT-29 colorectal tumor-bearing mice with median survival prolonged over 130 days and 90 days respectively, and prolonged the median survival of KRASG12C-mutant SW620 xenograft mice to 41 days[1]. p-SCN-Macropa-based radioimmunoconjugate [225Ac]Ac-macropa-Nimotuzumab (13 kBq; i.v.) exhibits prominent long-term retention in liver and blood of healthy BALB/c mice, and displays preferential accumulation in DLD-1 colorectal tumor xenografts with a peak uptake of 32.0 % IA/g at day 5 post-administration[1].
In Vitro, p-SCN-macropa conjugates to Nimotuzumab and Rituximab with high purity, forming macropa-Nimotuzumab with an estimated 3 p-SCN-macropa molecules per antibody[1]. p-SCN-Macropa-derived[225Ac]Ac-macropa-Nimotuzumab potently inhibits viability of 2D monolayer cultures of DLD-1 (IC50 1.8 nM), SNU-C2B (IC50 3.3 nM), SW620 (IC50 4.6 nM), and HT-29 (IC50 10.1 nM) colorectal cancer cell lines[1]. p-SCN-Macropa-derived[225Ac]Ac-macropa-Nimotuzumab potently inhibits viability of 3D spheroids of DLD-1 (IC50 10.6 nM), SNU-C2B (IC50 14.7 nM), SW620 (IC50 19.5 nM), and HT-29 (IC50 41.5 nM) colorectal cancer cells[1]. p-SCN-macropa (1 MBq/300 μg; 7 days), as a bifunctional chelator in [225Ac]Ac-macropa-Trastuzumab -PEG6-DM1, supports high radiochemical purity and excellent in vitro stability in human serum and PBS[2]. p-SCN-macropa-based [225Ac]Ac-macropa-trastuzumab-PEG6-DM1 binds with high affinity to HCC1954 (KD = 36.98 nM) and JIMT-1 (KD = 20.16 nM) HER2-positive breast cancer cells, with HER2 density-dependent internalization that is significantly higher in high HER2-density HCC1954 cells[2]. p-SCN-Macropa (5-10 mg/mL; 90 min at 37°C for conjugation, 5-10 min at room temperature for radiolabeling)-conjugated rosigatamab efficiently chelates 225Ac at room temperature within 5-10 min[3].
References:
[1]. Tikum AF, et al. Effectiveness of 225 Ac-Labeled Anti-EGFR Radioimmunoconjugate in EGFR-Positive Kirsten Rat Sarcoma Viral Oncogene and BRAF Mutant Colorectal Cancer Models. J Nucl Med. Published online February 15, 2024.
[2]. Pougoue Ketchemen J, et al. Highly potent [225Ac]Ac-macropa-trastuzumab-PEG6-DM1 antibody drug radioconjugate against HER2-positive breast cancer xenografts. J Nucl Med. 2024;65(suppl 2):242451.
[3]. Vallabhajosula S, et al. SCN-PYTA: A new bifunctional chelator (BFC) for trivalent radiometals to develop target-specific radiopharmaceuticals for imaging and therapy. Cancer Res. 2026;86(7 Suppl):Abstract 7183.
In Vivo, p-SCN-Macropa-containing radioimmunoconjugate [225Ac]Ac-macropa-Nimotuzumab (13 kBq per dose; i.v.; on days 0, 10, and 20) achieved complete tumor regression in 43% of KRASG12C-mutant DLD-1 and 14% of BRAFV600E-mutant HT-29 colorectal tumor-bearing mice with median survival prolonged over 130 days and 90 days respectively, and prolonged the median survival of KRASG12C-mutant SW620 xenograft mice to 41 days[1]. p-SCN-Macropa-based radioimmunoconjugate [225Ac]Ac-macropa-Nimotuzumab (13 kBq; i.v.) exhibits prominent long-term retention in liver and blood of healthy BALB/c mice, and displays preferential accumulation in DLD-1 colorectal tumor xenografts with a peak uptake of 32.0 % IA/g at day 5 post-administration[1].
In Vitro, p-SCN-macropa conjugates to Nimotuzumab and Rituximab with high purity, forming macropa-Nimotuzumab with an estimated 3 p-SCN-macropa molecules per antibody[1]. p-SCN-Macropa-derived[225Ac]Ac-macropa-Nimotuzumab potently inhibits viability of 2D monolayer cultures of DLD-1 (IC50 1.8 nM), SNU-C2B (IC50 3.3 nM), SW620 (IC50 4.6 nM), and HT-29 (IC50 10.1 nM) colorectal cancer cell lines[1]. p-SCN-Macropa-derived[225Ac]Ac-macropa-Nimotuzumab potently inhibits viability of 3D spheroids of DLD-1 (IC50 10.6 nM), SNU-C2B (IC50 14.7 nM), SW620 (IC50 19.5 nM), and HT-29 (IC50 41.5 nM) colorectal cancer cells[1]. p-SCN-macropa (1 MBq/300 μg; 7 days), as a bifunctional chelator in [225Ac]Ac-macropa-Trastuzumab -PEG6-DM1, supports high radiochemical purity and excellent in vitro stability in human serum and PBS[2]. p-SCN-macropa-based [225Ac]Ac-macropa-trastuzumab-PEG6-DM1 binds with high affinity to HCC1954 (KD = 36.98 nM) and JIMT-1 (KD = 20.16 nM) HER2-positive breast cancer cells, with HER2 density-dependent internalization that is significantly higher in high HER2-density HCC1954 cells[2]. p-SCN-Macropa (5-10 mg/mL; 90 min at 37°C for conjugation, 5-10 min at room temperature for radiolabeling)-conjugated rosigatamab efficiently chelates 225Ac at room temperature within 5-10 min[3].
References:
[1]. Tikum AF, et al. Effectiveness of 225 Ac-Labeled Anti-EGFR Radioimmunoconjugate in EGFR-Positive Kirsten Rat Sarcoma Viral Oncogene and BRAF Mutant Colorectal Cancer Models. J Nucl Med. Published online February 15, 2024.
[2]. Pougoue Ketchemen J, et al. Highly potent [225Ac]Ac-macropa-trastuzumab-PEG6-DM1 antibody drug radioconjugate against HER2-positive breast cancer xenografts. J Nucl Med. 2024;65(suppl 2):242451.
[3]. Vallabhajosula S, et al. SCN-PYTA: A new bifunctional chelator (BFC) for trivalent radiometals to develop target-specific radiopharmaceuticals for imaging and therapy. Cancer Res. 2026;86(7 Suppl):Abstract 7183.