Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 1 shows the chemical structure of DOTAMTATE and biodistribution of 212Pb-DOTAMTATE in athymic nude tumor bearing mice.

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques:

Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 2 shows a biodistribution of 212Pb-DOTAMTATE in CD-1 mice at 1-hour post drug injection with kidney protection agents. 200μL of kidney protections agents 7mg Arg-7mg Lys in saline (red), 7mg Lys in saline (green), 14mg Lys in saline (blue), 14mg Arg in saline (purple) or 7mg Arg-7mg Lys in 10% dextrose (orange) were given IP five minutes before drug injection. No kidney protection agent control shown in black. 5 mice per group. Average of two studies displayed.

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques: Injection, Saline, Control

Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 3 shows radio HPLC and biodistribution studies of 212Pb-DOTAMTATE with ascorbic acid. A. Radio-HPLC of 212Pb-DOTAMTATE without ascorbic acid present during chelation (orange) or with 10mM final concentration of ascorbic acid (blue) prior to biodistribution. B. Biodistribution of 212Pb-DOTAMTATE in AR42J tumor bearing mice (n=5 per group) at 1hr, 4hr and 24hrs post drug injection in the presence of 10mM ascorbic acid (blue) or none (orange).

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques: Concentration Assay, Injection

Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 4 shows initial dose range finding studies and fractionated dose toxicity studies with 212Pb-DOTAMTATE in athymic nude mice. A. Kaplan-Meier survival curve of 212Pb-DOTAMTATE treated athymic nude mice. Animals received a single dose of 10μCi (purple), 20μCi (blue), 40μCi (green), or 60μCi (red) of 212Pb-DOTAMTATE or PBS control (black). n=5 mice per group. Survival of the animals are shown in days post injection during the 4-week study. B. Kaplan-Meier curve of 212Pb-DOTAMTATE in CD-1 mice in a fractionated dose toxicity study. PBS alone, n=10 (black), 1 × 40μCi, n=10 (red), 2 × 20μCi, n=10 (green) and 3 ×15μCi, n=10 (blue) treatment groups. Drug cycles 1, 2 and 3 are shown with grey dots.

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques: Control, Injection

Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 5 shows the efficacy of mice treated with 212Pb-DOTAMTATE in a single and multi-injection dose setting. Groups of animals were injected with cold DOTAMTATE (n=8), PBS (n=8), 5μCi 212Pb-DOTAMTATE (n=9), 10μCi 212Pb-DOTAMTATE (n=8), 2 × 5μCi 212Pb-DOTAMTATE (n=18), Tumor volumes for individual mice per group are shown in mm3 over time.

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques: Injection

Journal: Molecular cancer therapeutics

Article Title: Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model

doi: 10.1158/1535-7163.MCT-18-1103

Figure Lengend Snippet: Figure 6 shows an efficacy study of AR42J tumor bearing mice treated with 212Pb-DOTAMTATE in combination with 5-fluorouracil. A. Individual mouse efficacy data showing tumor volumes of mice injected with saline (black), 5-FU only (red), 212Pb-DOTAMTATE only (blue) and in combination with 5-FU (green). B. Kaplan Meier of animals treated with saline (black), 5-FU only (red), 212Pb-DOTAMTATE only at 2-week intervals (blue dashed), 3-week intervals (blue solid), in combination with 5-FU at 2-week intervals (green dashed) or three-week intervals (green solid).

Article Snippet: Manufacturing and Radiolabeling GMP DOTAMTATE (C 65 H 93 N 17 O 16 S 2 , ) was manufactured by Macrocyclics using Fmoc solid phase peptide synthesis.

Techniques: Injection, Saline