| 2. |
- Hasnowo, Lutfi A., et al.
(författare)
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Synthesis, I-123-Radiolabeling Optimization, and Initial Preclinical Evaluation of Novel Urea-Based PSMA Inhibitors with a Tributylstannyl Prosthetic Group in Their Structures
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:15
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine & epsilon;-nitrogen atom, a dipeptide including two phenylalanine residues in the L-configuration as the peptide fragment of the linker, and 3- or 4-(tributylstannyl)benzoic acid as a prosthetic group in their structures for radiolabeling. The standard compounds [I-127]PSMA-m-IB and [I-127]PSMA-p-IB for comparative and characterization studies were first synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach, in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence followed by replacement of the Sn(Bu)(3) group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [I-123]PSMA-p-IB was higher than that of [I-123]PSMA-m-IB, which were 74.9 & PLUSMN; 1.0% and 49.4 & PLUSMN; 1.2%, respectively. The radiochemical purity of [I-123]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [I-123]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [I-123]PSMA-p-IB showed less accumulation than [Lu-177]Lu-PSMA-617 in several normal organs (liver, kidney, and bone). These results warrant further preclinical development, including toxicology evaluation and experiments in tumor-bearing mice.
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| 3. |
- Apollonio, M., et al.
(författare)
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Beam Dynamics of the Transparent Injection for the MAX IV 1.5 GeV Ring
- 2022
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Ingår i: Proc. IPAC'22. - 9783954502271 ; , s. 284-287
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Following the successful operation of the Multipole Injection Kicker (MIK) in the MAX IV 3 GeV storage ring, we plan to introduce a similar device in the MAX IV 1.5 GeV ring. In order to assess the effectiveness of such device and to define its working parameters, we performed a series of studies aimed at understanding the beam dynamics related to the injection process. In this paper we describe the optimization of the MIK working parameters, we study the resilience to tune shifts for a chosen injection scheme and illustrate some tests conducted to evaluate the ring acceptance. We conclude with remarks about the effects of magnet errors on key performance parameters such as the injection efficiency and perturbations to the size and divergence of the stored beam and a brief discussion on future work.
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