Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging
Abstract
1. Introduction
2. Experimental Section
2.1. Materials and Methods
2.2. Synthesis of Rhenium Complexes
2.2.1. Synthesis of Complex fac-[Re(CO)3(Cip-DTC)(H2O)] (1)
2.2.2. Synthesis of fac-[Re(CO)3(Cip-DTC)(PPh3)] (2)
2.2.3. One-Pot Synthesis of Rhenium Complexes 3–6 Using Re(CO)5Br
2.3. Preparation of Technetium-99m Complexes
2.3.1. Synthesis of Intermediate Complex fac-[99mTc(CO)3(Cip-DTC)(H2O)] (1′)
2.3.2. Synthesis of fac-[99mTc(CO)3(Cip-DTC)(P)] Complexes (2′–6′)
2.4. Stability Studies for 99mTc-Complexes
2.4.1. Stability in Reaction Mixture
2.4.2. Stability of Purified Complexes
2.4.3. Cysteine and Histidine Challenge Studies
2.5. Lipophilicity Studies for 99mTc-Complexes
2.6. Biodistribution Studies for 99mTc-Complexes
3. Results and Discussion
3.1. Preparation of Rhenium Complexes
3.2. Preparation of 99mTc-Complexes
3.3. Stability Studies
3.4. Lipophilicity Studies
3.5. Biodistribution Studies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Position | Cip | Cip-DTC | 1 | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|---|---|
H-2/H-5 | 2.90 | 4.57 | 4.11 | 3.60 | 3.67 3.58 | 3.76 3.47 | 3.85 | 4.15 3.99 |
H-3/H4 | 3.24 | 3.17 | 3.44 | 3.27 2.89 | 3.34 2.80 | 3.39 3.09 | 3.43 3.19 | 3.45 3.32 |
H-7 | 7.54 | 7.42 | 7.58 | 7.39 | 7.37 | 7.48 | 7.48 | 7.44 |
H-10 | 7.90 | 7.80 | 7.92 | 7.81 | 7.81 | 7.88 | 7.87 | 7.82 |
H-12 | 8.66 | 8.54 | 8.63 | 8.54 | 8.53 | 8.60 | 8.59 | 8.55 |
H-16 | 3.83 | 3.61 | 3.75 | 3.65 | 3.57 | 3.72 | 3.70 | 3.57 |
H-17/H-18 | 1.31 1.18 | 1.28 1.00 | 1.33 1.15 | 1.30 1.04 | 1.30 1.02 | 1.32 1.11 | 1.32 1.08 | 1.27 1.00 |
P–Ph3 | 7.51 7.44 | 7.32 7.28 7.05 6.84 | 7.56 7.48 | 7.56 7.47 7.40 | ||||
P–CH3 | 2.28 | 1.93 | ||||||
O–CH3 | 3.71 | |||||||
NCH2N | 4.47 | |||||||
PCH2N | 4.20 |
Compound | M: Re | M: 99mTc | |
---|---|---|---|
(tR min) | (tR min) | LogD7.4 | |
fac-[M(CO)3(Cip-DTC)(H2O)] (1, 1′) | 16.8 | 17.1 | 1.2 |
fac-[M(CO)3(Cip-DTC)(PPh3)] (2, 2′) | 26.1 | 26.4 | 2.3 |
fac-[M(CO)3(Cip-DTC)(TMPP)] (3, 3′) | 27.1 | 27.5 | 2.7 |
fac-[M(CO)3(Cip-DTC)(MePPh2)] (4, 4′) | 23.2 | 23.6 | 1.8 |
fac-[M(CO)3(Cip-DTC)(DMPP)] (5, 5′) | 22.3 | 22.7 | 2.0 |
fac-[M(CO)3(Cip-DTC)(ADAP)] (6, 6′) | 17.1 | 17.3 | 1.6 |
Tissue | 1′ | 2′ | 3′ | |||
---|---|---|---|---|---|---|
15 min | 120 min | 15 min | 120 min | 15 min | 120 min | |
Blood | 14.07 ± 0.83 | 7.76 ± 0.29 | 4.51 ± 1.32 | 5.19 ± 0.81 | 2.54 ± 0.25 | 6.71 ± 0.50 |
Liver | 22.05 ± 1.40 | 25.96 ± 2.23 | 32.36 ± 3.58 | 27.16 ± 4.02 | 47.48 ± 1.30 | 27.58 ± 0.66 |
Heart | 1.93 ± 0.23 | 1.58 ± 0.21 | 1.23 ± 0.36 | 3.97 ± 0.25 | 0.74 ± 0.32 | 3.48 ± 0.23 |
Kidneys | 5.16 ± 0.32 | 5.76 ± 0.65 | 1.30 ± 0.13 | 6.50 ± 0.36 | 1.40 ± 0.57 | 5.65 ± 0.78 |
Stomach | 0.91 ± 0.20 | 1.42 ± 0.30 | 0.55 ± 0.23 | 1.23 ± 0.14 | 0.64 ± 0.61 | 1.21 ± 0.32 |
Intestines | 0.71 ± 0.11 | 1.81 ± 0.15 | 0.14 ± 0.03 | 1.08 ± 0.07 | 0.36 ± 0.25 | 3.52 ± 0.19 |
Spleen | 9.79 ± 1.69 | 5.24 ± 0.45 | 38.44 ± 3.92 | 37.02 ± 4.43 | 33.88 ± 2.81 | 23.10 ± 1.74 |
Muscle | 0.18 ± 0.02 | 0.18 ± 0.01 | 0.90 ± 0.09 | 0.68 ± 0.05 | 0.13 ± 0.05 | 0.34 ± 0.02 |
Lungs | 6.41 ± 1.14 | 4.33 ± 0.41 | 6.66 ± 1.45 | 10.20 ± 0.12 | 9.58 ± 0.86 | 8.67 ± 0.72 |
Pancreas | 0.91 ± 0.04 | 0.82 ± 0.06 | 0.47 ± 0.20 | 1.04 ± 0.04 | 0.29 ± 0.13 | 0.93 ± 0.20 |
Infection | 1.06 ± 0.20 | 1.80 ± 0.39 | 2.93 ± 0.09 | 3.12 ± 0.14 | 0.27 ± 0.11 | 1.14 ± 0.05 |
Aseptic Infl. | 0.78 ± 0.51 | 1.33 ± 0.09 | 1.21 ± 0.07 | 0.86 ± 0.10 | 0.15 ± 0.07 | 0.52 ± 0.23 |
Urine * | 0.15 ± 0.08 | 1.57 ± 0.98 | 3.95 ± 1.30 | 4.04 ± 1.23 | 0.00 ± 0.00 | 0.01 ± 0.02 |
Tissue | 4′ | 5′ | 6′ | |||
---|---|---|---|---|---|---|
15 min | 120 min | 15 min | 120 min | 15 min | 120 min | |
Blood | 3.20 ± 0.47 | 1.48 ± 0.11 | 0.91 ± 0.03 | 0.66 ± 0.05 | 2.18 ± 0.06 | 1.33 ± 0.10 |
Liver | 42.11 ± 1.70 | 31.09 ± 0.72 | 35.51 ± 0.97 | 31.27 ± 5.71 | 20.95 ± 1.56 | 22.98 ± 2.70 |
Heart | 4.36 ± 0.46 | 8.85 ± 0.63 | 2.98 ± 0.46 | 4.30 ± 1.47 | 4.27 ± 0.42 | 1.94 ± 0.31 |
Kidneys | 5.92 ± 0.60 | 11.10 ± 0.70 | 3.20 ± 0.35 | 5.69 ± 1.44 | 8.05 ± 0.22 | 4.47 ± 0.52 |
Stomach | 1.11 ± 0.50 | 2.23 ± 0.37 | 0.53 ± 0.22 | 2.33 ± 0.44 | 0.98 ± 0.29 | 3.14 ± 0.69 |
Intestines | 1.27 ± 0.16 | 7.97 ± 0.12 | 0.61 ± 0.17 | 9.98 ± 1.22 | 3.22 ± 0.32 | 10.24 ± 1.11 |
Spleen | 21.59 ± 0.98 | 8.14 ± 0.93 | 18.04 ± 0.73 | 7.64 ± 1.22 | 6.40 ± 0.66 | 2.55 ± 0.27 |
Muscle | 0.56 ± 0.07 | 1.48 ± 0.05 | 0.40 ± 0.06 | 1.34 ± 0.09 | 1.01 ± 0.12 | 0.69 ± 0.05 |
Lungs | 11.15 ± 0.19 | 9.41 ± 1.15 | 9.87 ± 0.89 | 5.37 ± 0.47 | 7.13 ± 0.35 | 3.06 ± 0.10 |
Pancreas | 1.38 ± 0.21 | 3.21 ± 0.28 | 0.83 ± 0.18 | 3.68 ± 0.48 | 3.70 ± 0.26 | 2.27 ± 0.37 |
Infection | 0.88 ± 0.15 | 2.83 ± 0.30 | 0.94 ± 0.31 | 3.10 ± 0.46 | 0.94 ± 0.09 | 0.69 ± 0.09 |
Aseptic Infl. | 0.77 ± 0.12 | 1.88 ± 0.26 | 0.51 ± 0.14 | 2.37 ± 0.34 | 1.10 ± 0.06 | 0.66 ± 0.10 |
Urine * | 0.01 ± 0.00 | 0.04 ± 0.03 | 0.03 ± 0.01 | 0.32 ± 0.12 | 0.37 ± 0.08 | 1.49 ± 0.23 |
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Papasavva, A.; Pirmettis, N.N.; Shegani, A.; Papadopoulou, E.; Kiritsis, C.; Georgoutsou-Spyridonos, M.; Mastellos, D.C.; Chiotellis, A.; Kyprianidou, P.; Pelecanou, M.; et al. Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging. Pharmaceutics 2024, 16, 1210. https://doi.org/10.3390/pharmaceutics16091210
Papasavva A, Pirmettis NN, Shegani A, Papadopoulou E, Kiritsis C, Georgoutsou-Spyridonos M, Mastellos DC, Chiotellis A, Kyprianidou P, Pelecanou M, et al. Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging. Pharmaceutics. 2024; 16(9):1210. https://doi.org/10.3390/pharmaceutics16091210
Chicago/Turabian StylePapasavva, Afroditi, Nektarios N. Pirmettis, Antonio Shegani, Eleni Papadopoulou, Christos Kiritsis, Maria Georgoutsou-Spyridonos, Dimitrios C. Mastellos, Aristeidis Chiotellis, Patricia Kyprianidou, Maria Pelecanou, and et al. 2024. "Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging" Pharmaceutics 16, no. 9: 1210. https://doi.org/10.3390/pharmaceutics16091210
APA StylePapasavva, A., Pirmettis, N. N., Shegani, A., Papadopoulou, E., Kiritsis, C., Georgoutsou-Spyridonos, M., Mastellos, D. C., Chiotellis, A., Kyprianidou, P., Pelecanou, M., Papadopoulos, M., & Pirmettis, I. (2024). Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging. Pharmaceutics, 16(9), 1210. https://doi.org/10.3390/pharmaceutics16091210