Structure of FAP-2286
CAS No.: 2581741-18-4
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| CAS No. : | 2581741-18-4 |
| Formula : | C67H99N13O18S3 |
| M.W : | 1470.77 |
| SMILES Code : | O=C1[C@]2(N(C(=O)[C@@H](NC(CCCCC)=O)CSCC=3C=C(C=C(CSCCNC(CN4CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC4)=O)C3)CSC[C@@H](C(O)=O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@]([C@@H](C)O)(NC(=O)[C@]6(N1CCC6)[H])[H])CCC2)[H] |
| English Name : | 2,2',2''-(10-(2-((2-((((12S,32S,5R,13R,16S,19S,22S)-19-(3-Amino-3-oxopropyl)-16-benzyl-13-carboxy-5-hexanamido-22-((R)-1-hydroxyethyl)-2,4,15,18,21,24-hexaoxo-7,11-dithia-14,17,20,23-tetraaza-1(1,2),3(2,1)-dipyrrolidina-9(1,3)-benzenacyclotetracosaphane-95-yl)methyl)thio)ethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid |
| MDL No. : | N/A |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 11.0 mg | With triisopropylsilane; water; ethane-1,2-dithiol; trifluoroacetic acid for 2h; | 1.B; 2.2b Cleavage method B: Cleavage of unprotected fragments (complete resin cleavage): General procedure: After the completion of the assembly of the sequence the resin was finally washed with DCM (3 ml, 4x 1 minute), dried in the vacuum overnight and treated with TFA, EDT, water and TIPS (94/2.5/2.5/1) for 2 h (unless otherwise stated). Afterwards the cleavage solution was poured into a chilled mixture of MTBE and cyclohexane (1/1, 10- fold excess compared to the volume of cleavage solution), centrifuged at 4 °C for 5 minutes and the precipitate collected and dried in the vacuum. The residue was lyophilized from water/ acetonitrile prior to purification or further modification. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77.4% | With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide | 8a Example 8a): Synthesis of Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]- OH (3BP-3554) To the solution of Hex-[Cys(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (19.5 mg, 18 pmol, 3BP-4089 - described in Example 7a) in 300 m DMSO, 5 m DIPEA were added to adjust the pH value to approximately 7.5 - 8. Then 20.5 mg of DOTA-NHS (27 pmol, 1.5 eq compared to the peptide intermediate) in 200 pi DMSO were added. During the course of the LC/TOF- MS monitored reaction 5 pi DIPEA was added 3 times to re-adjust the pH value to the starting value. After reaction completion the solution was subjected to HPLC purification (15 to 45% B in 30 min - Kinetex) to yield 20.44 mg of the pure title compound (77.4 % yield). HPLC: Rt = 5.9 min. LC/TOF-MS: exact mass 1469.640 (calculated 1469.639). C67H99N13O18S3 (MW = 1470.780). |
| 20.44 mg | With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide | 2.2a Example 2a: Synthesis by two alternative cyclization methods in solution Both cyclization methods perform similarly and achieve comparable yields and similar purities. To the solution of the intermediate Hex-[Cys(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (in this example obtained by cyclization method B) in 300 pi DMSO, 5 pi DIPEA were added to adjust the pH value to approximately 7.5 - 8. Then 20.5 mg of DOTA-NHS (27 pmol, 1.5 eq compared to the peptide intermediate) in 20( were added. During the course of the LC/TOF-MS monitored reaction 5 pi DIPEA were added 3 times to re-adjust the pH value to the starting value. After reaction completion the solution was subjected to HPLC purification * I .' so 45' 1 30 min - Kinetex) to yield 20.44 mg of the pure title compound (27.8% overall yield). HPLC: Rt = 5.9 min. LC/TOF-MS: exact mass 1469.640 (calculated 1469.639). C67H99N13O18S3 (MW = 1470.780). |
| 77.4 % | With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide | 8a Example 8a): Synthesis of Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]- OH (3BP-3554) To the solution of Hex-[Cys(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (19.5 mg, 18 pmol, 3BP-4089 - described in Example 7a) in 300 m DMSO, 5 m DIPEA were added to adjust the pH value to approximately 7.5 - 8. Then 20.5 mg of DOTA-NHS (27 pmol, 1.5 eq compared to the peptide intermediate) in 200 pi DMSO were added. During the course of the LC/TOF- MS monitored reaction 5 pi DIPEA was added 3 times to re-adjust the pH value to the starting value. After reaction completion the solution was subjected to HPLC purification (15 to 45% B in 30 min - Kinetex) to yield 20.44 mg of the pure title compound (77.4 % yield). HPLC: Rt = 5.9 min. LC/TOF-MS: exact mass 1469.640 (calculated 1469.639). C67H99N13O18S3 (MW = 1470.780). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | With sodium acetate at 50℃; for 0.333333h; | 28.F A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 81 % | With sodium acetate at 50℃; | 28.F A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 51% | With sodium acetate at 50℃; for 0.333333h; | 28.H A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 51 % | With sodium acetate at 50℃; | 28.H A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | With sodium acetate at 50℃; for 0.333333h; | 28.G A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 82 % | With sodium acetate at 50℃; | 28.G A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With ammonium acetate at 20℃; | 28.I A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 83 % | With ammonium acetate at 20℃; | 28.I A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | With sodium acetate at 50℃; for 0.333333h; | 28.J A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 88 % | With sodium acetate at 50℃; | 28.J A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With sodium acetate at 50℃; for 0.333333h; | 28.K A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| 77 % | With sodium acetate at 50℃; | 28.K A. General procedure for the preparation of a peptide comprising DOTA-transition metal- complexes from corresponding peptides comprising uncomplexed DOTA General procedure: A 0.1 mM solution of the peptide comprised by uncomplexed DOTA in • 0.4 M sodium acetate, pH = 5 (Buffer A) (in case of Cu(II), Zn(II), In(III), Lu(III) or Ga(III) complexes) or • 0.1 M ammonium acetate, pH = 8 (Buffer B) (in case of Eu(III) complexes) was diluted with a solution 0.1 mM solution of the corresponding metal salt in water whereby the molar ratio of peptide to metal was adjusted to 1 : 3. The solution was stirred • at 50 °C for 20 minutes (also referred to herein as Condition A) (in case of In(III), Lu(III), Ga(III), Zn(II) or Cu(II) complexes) or • at room temperature overnight (also referred to herein as Condition B) (in case of Eu(III) complexes). The solution was then applied to • HPLC purification (also referred to herein as Purification A) or • solid phase extraction (also referred to herein as Purification B). In case of solid phase extraction 250 mg Varian Bondesil-ENV was placed in a 15 ml polystyrene syringe, pre-washed with methanol (1 x 5 ml) and water (2 x 5 ml). Then the reaction solution was applied to the column. Thereafter elution was performed with water (2 x 5 ml - to remove excess salt), 5 ml of 50% ACN in water as first fraction and each of the next fractions were eluted with 5 ml of 50% ACN in water containing 0.1% TFA. In either case (HPLC purification or solid phase extraction) fractions containing the pure product were pooled and freeze dried. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 63% | With trifluoroacetic acid In dimethyl sulfoxide at 90℃; for 0.5h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With trifluoroacetic acid In dimethyl sulfoxide at 90℃; for 0.5h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In aq. buffer at 90℃; for 0.166667h; | 1 177Lu-Compound I for injection is manufactured through the complexation of 177Lu(III) toCompound I followed immediately by formulation and filtration through a 0.22 um membraneinto a pre-sterilized vial. For the complexation step, the following process is used. To a solutionof 177LuCl3 is added radiolabeling buffer (comprising, e.g., ~74 mg/mL Sodium Acetate; ~ 18mg/mL Ascorbic Acid; ~ 25 mg/mL N-Acetyl-L-cysteine) such that 100 uL of buffer is added foreach 1 GBq of activity. To the 177LuCl3 solution is added the precursor (Compound I, ~310 ug)dissolved in sterile water for injection (SWFI, 0.3 mL). The mixture is heated to 90 + 5 for 10+ 1 minute while mixing. The reaction mixture is diluted with formulation buffer such that thefinal volume of formulated product is approx. 22 mL. The formulation buffer comprises ~0.2mg/mL DTPA, ~100 mg/mL Ascorbic Acid, ~40 mg/mL N-Acetyl-L-cysteine, ~33 mg/mLsodium hydroxide, ~44 mg/mL ethanol in SWFI. |