advanced accelerator applications usa, inc - Medication Listings

11.1 Chemical Characteristics LOCAMETZ (kit for the preparation of gallium Ga 68 gozetotide injection) is a sterile, radioactive diagnostic agent for intravenous administration after radiolabeling. Each vial contains 25 micrograms of gozetotide, 1 mg gentisic acid, 78 mg of sodium acetate trihydrate, and 40 mg sodium chloride. Gozetotide is also known as PSMA-11. After reconstitution and radiolabeling of LOCAMETZ, the vial contains gallium Ga 68 gozetotide injection at a radioactivity of up to 2,590 MBq (70 mCi) in up to 10 mL at calibration date and time. The vial also contains hydrochloric acid derived from the gallium-68 chloride solution. Gallium Ga 68 gozetotide injection has a pH between 3.2 to 6.5. Gallium Ga 68 gozetotide is a urea based peptidomimetic that has a covalently bound chelator (HBED-CC). The peptide has amino acid sequence OH-Glu-CO-Lys(Ahx-CC-HBED)-OH. Gallium Ga 68 gozetotide has a molecular weight of 1011.91 g/mol. The chemical structure is shown in Figure 3. Figure 3. Chemical Structure of Gallium Ga 68 Gozetotide 11.2 Physical Characteristics Gallium-68 decays with a half-life of 68 minutes to stable zinc-68. Table 4 and Table 5 display the principle radiation emission data, and physical decay of gallium-68. Table 4. Principal Radiation Emission Data (> 1%) for Gallium-68 Radiation/Emission % Disintegration Mean energy (MeV) beta+ 88% 0.8360 beta+ 1.1% 0.3526 Gamma 178% 0.5110 Gamma 3% 1.0770 X-ray 2.8% 0.0086 X-ray 1.4% 0.0086 Table 5. Physical Decay Chart for Gallium-68 Minutes Fraction remaining 0 1 15 0.858 30 0.736 60 0.541 90 0.398 120 0.293 180 0.158 240 0.086 360 0.025 11.3 Radiation Attenuation Table 6 displays the radiation attenuation by lead shielding of gallium-68. Table 6. Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding Shield thickness (Pb) mm Coefficient of attenuation 6 0.5 12 0.25 17 0.1 34 0.01 51 0.001 Figure 4. Chemical Structure of Gozetotide

Lutetium Lu 177 dotatate is a radiolabeled somatostatin analog. The drug substance lutetium Lu 177 dotatate is a cyclic peptide linked with the covalently bound chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to a radionuclide. Lutetium Lu 177 dotatate is described as lutetium (Lu 177)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl) acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic (2-7) disulfide. The molecular weight is 1609.6 Daltons and the structural formula is as follows: LUTATHERA (lutetium Lu 177 dotatate) 370 MBq/mL (10 mCi/mL) Injection is a sterile, clear, colorless to slightly yellow solution for intravenous use. Each single-dose vial contains acetic acid (0.48 mg/mL), sodium acetate (0.66 mg/mL), gentisic acid (0.63 mg/mL), sodium hydroxide (0.64 mg/mL), ascorbic acid (2.8 mg/mL), diethylene triamine pentaacetic acid (0.05 mg/mL), sodium chloride (6.85 mg/mL), and Water for Injection (ad 1 mL). The pH range of the solution is 4.5 to 6. Lutetium Lu 177 dotatate structural formula 11.1 Physical Characteristics Lutetium-177 decays to stable hafnium-177 with a half-life of 6.647 days, by emitting beta-minus radiation with a maximum energy of 0.498 MeV (79%) and photonic radiation (γ) of 0.208 MeV (11%) and 0.113 MeV (6.2%). The main radiations of lutetium-177 are detailed in Table 7. Table 7. Lutetium-177 Main Radiations Radiation Energy (keV) Iβ - % Iγ% β - 176.5 12.2 β - 248.1 0.05 β - 384.9 9.1 β - 497.8 78.6 γ 71.6 0.15 γ 112.9 6.20 γ 136.7 0.05 γ 208.4 11.0 γ 249.7 0.21 γ 321.3 0.22 11.2 External Radiation Table 8 summarizes the radioactive decay properties of lutetium-177. Table 8. Physical Decay Chart: Lutetium-177 Physical Half-Life = 6.647 Days Hours Fraction remaining Hours Fraction remaining 0 1.000 48 (2 days) 0.812 1 0.996 72 (3 days) 0.731 2 0.991 168 (7 days) 0.482 5 0.979 336 (14 days) 0.232 10 0.958 720 (30 days) 0.044 24 (1 day) 0.901 1080 (45 days) 0.009

NETSPOT is supplied as a sterile, multiple-dose kit for preparation of gallium Ga 68 dotatate injection for intravenous use. Dotatate, also known as DOTA-0-Tyr3-Octreotate, is a cyclic 8 amino acid peptide with a covalently bound chelator (dota). The peptide has the amino acid sequence: H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH, and contains one disulfide bond. Dotatate has a molecular weight of 1435.6 Daltons and its chemical structure is shown in Figure 3. Figure 3. Chemical Structure of Dotatate [(4,7,10-Tricarboxymethyl-1,4,7,10-tetrazacyclododec-1-yl)acetyl]-(D)-Phenylalanyl-(L)Cysteinyl-(L)-Tyrosyl-(D)-Tryptophanyl-(L)-Lysyl-(L)-Threoninyl-(L)-Cysteinyl-(L)-Threonine-cyclic(2-7)disulfide NETSPOT is a kit with the following components: Vial 1 (reaction vial with lyophilized powder) contains: 40 mcg dotatate, 5 mcg 1,10-phenanthroline; 6 mcg gentisic acid; 20 mg mannitol. Vial 2 (buffer vial) contains: 60 mg formic acid; 56.5 mg sodium hydroxide and water for injection. After radiolabeling, [see Dosage and Administration ( 2.3 )] , gallium Ga 68 dotatate injection also contains hydrochloric acid as an excipient derived from the generator eluate. The prepared gallium Ga 68 dotatate injection for intravenous use, is a sterile, pyrogen free, clear, colorless, buffered solution, with a pH between 3.2 and 3.8. Table 5, Table 6, and Table 7 display the principal radiation emission data, radiation attenuation by lead shielding, and physical decay of gallium-68. Table 5. Principal Radiation Emission Data (> 1%) Radiation/Emission % Disintegration Mean energy (MeV) beta+ 88% 0.8360 beta+ 1.1% 0.3526 gamma 178% 0.5110 gamma 3% 1.0770 X-ray 2.8% 0.0086 X-ray 1.4% 0.0086 Table 6. Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding Shield thickness (Pb) mm Coefficient of attenuation 6 0.5 12 0.25 17 0.1 34 0.01 51 0.001 Table 7. Physical Decay Chart for Gallium-68 Minutes Fraction remaining 0 1.000 15 0.858 30 0.736 60 0.541 90 0.398 120 0.293 180 0.158 360 0.025 Figure 3. Chemical Structure of dotatate

PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) is a radioligand therapeutic agent. Lutetium Lu 177 vipivotide tetraxetan is a PSMA-binding ligand bound to a DOTA chelator radiolabeled with lutetium-177. The chemical name is 2-[4-[2-[[4-[[(2S)-1-[[(5S)-5-carboxy-5-[[(1S)-1,3-dicarboxy propyl]carbamoylamino]pentyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]cyclohexyl]methylamino]-2-oxoethyl]-4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate; lutetium-177(3+). The molecular mass is 1216.06 g/mol and the molecular formula is C 49 H 68 177 LuN 9 O 16 . The chemical structure for lutetium Lu 177 vipivotide tetraxetan is shown below: PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) 1,000 MBq/mL (27 mCi/mL) Injection is supplied as a sterile, clear, colorless to slightly yellow solution for intravenous use. Each single-dose vial contains acetic acid (0.30 mg/mL), sodium acetate (0.41 mg/mL), gentisic acid (0.39 mg/mL), sodium ascorbate (50.0 mg/mL), pentetic acid (0.10 mg/mL), and water for injection (q.s. to 1 mL). The pH range of the solution is 4.5 to 7.0. Chemical Structure of lutetium 11.1 Physical Characteristics Lutetium-177 decays to a stable hafnium-177 with a physical half-life of 6.647 days by emitting beta-minus radiation with a maximum energy of 498 keV (79%) and photonic radiation (γ) of 208 keV (11%) and 113 keV (6.4%). The main radiations of lutetium-177 are detailed in Table 7. Table 7: Lutetium-177 Main Radiations Radiation Energy (keV) Iβ - % Iγ% β - 176.5 12.2 β - 248.1 0.05 β - 384.9 9.1 β - 497.8 78.6 γ 71.6 0.15 γ 112.9 6.40 γ 136.7 0.05 γ 208.4 11.0 γ 249.7 0.21 γ 321.3 0.22 11.2 External Radiation Table 8 summarizes the radioactive decay properties of lutetium-177. Table 8: Physical Decay Chart: Lutetium-177 Physical Half-life = 6.647 days Hours Fraction remaining 0 1.000 1 0.996 2 0.991 5 0.979 10 0.958 24 (1 day) 0.901 48 (2 days) 0.812 72 (3 days) 0.731 120 (5 days) 0.594 168 (7 days) 0.482 336 (14 days) 0.232 720 (30 days) 0.044 1080 (45 days) 0.009