| 000 | 03713nlm1a2200505 4500 | ||
|---|---|---|---|
| 001 | 664014 | ||
| 005 | 20231030041915.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\35184 | ||
| 035 | _aRU\TPU\network\33714 | ||
| 090 | _a664014 | ||
| 100 | _a20210323a2020 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aHeterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer—Optimization of the Affinity towards PSMA by Linker Modification in Murine Model _fF. Lundmark, A. Abouzayed, B. Mitran [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: 29 tit.] | ||
| 330 | _aProstate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) are promising targets for molecular imaging of prostate cancer (PCa) lesions. Due to the heterogenic overexpression of PSMA and GRPR in PCa, a heterodimeric radiotracer with the ability to bind to both targets could be beneficial. Recently, our group reported the novel heterodimer BQ7800 consisting of a urea-based PSMA inhibitor, the peptide-based GRPR antagonist RM26 and NOTA chelator. The study reported herein, aimed to improve the affinity of BQ7800 towards PSMA by changing the composition of the two linkers connecting the PSMA- and GRPR-targeting motifs. Three novel heterodimeric analogues were synthesized by incorporation of phenylalanine in the functional linker of the PSMA-binding motif and/or shortening the PEG-linker coupled to RM26. The heterodimers were labeled with indium-111 and evaluated in vitro. In the competitive binding assay, BQ7812, featuring phenylalanine and shorter PEG-linker, demonstrated a nine-fold improved affinity towards PSMA. In the in vivo biodistribution study of [111In]In-BQ7812 in PC3-pip tumor-bearing mice (PSMA and GRPR positive), the activity uptake was two-fold higher in the tumor and three-fold higher in kidneys than for [111In]In-BQ7800. Herein, we showed that the affinity of a bispecific PSMA/GRPR heterodimer towards PSMA could be improved by linker modification. | ||
| 461 | _tPharmaceutics | ||
| 463 |
_tVol. 12, iss. 7 _v[614, 15 p.] _d2020 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aprostate cancer | |
| 610 | 1 | _aPSMA | |
| 610 | 1 | _aGRPR | |
| 610 | 1 | _aheterodimer | |
| 610 | 1 | _amolecular imaging | |
| 610 | 1 | _aSPPS | |
| 610 | 1 | _aрак | |
| 610 | 1 | _aвизуализация | |
| 701 | 1 |
_aLundmark _bF. _gFanny |
|
| 701 | 1 |
_aAbouzayed _bA. _gAyman |
|
| 701 | 1 |
_aMitran _bB. _gBogdan |
|
| 701 | 1 |
_aRinne _bS. S. _gSara |
|
| 701 | 1 |
_aVarasteh _bZ. _gZohreh |
|
| 701 | 1 |
_aLarhed _bM. _gMats |
|
| 701 | 1 |
_aTolmachev _bV. M. _cspecialist in the field of medical technology _cDirector of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D _f1961- _gVladimir Maksimilianovich _2stltpush _3(RuTPU)RU\TPU\pers\46552 |
|
| 701 | 1 |
_aRosenstrom _bU. _gUlrika |
|
| 701 | 1 |
_aOrlova _bA. M. _cspecialist in the field of medical technology _cSenior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D _f1960- _gAnna Markovna _2stltpush _3(RuTPU)RU\TPU\pers\46554 |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИсследовательская школа химических и биомедицинских технологий _bНаучно-исследовательский центр "Онкотераностика" _h8442 _2stltpush _3(RuTPU)RU\TPU\col\27561 |
| 801 | 2 |
_aRU _b63413507 _c20210323 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.3390/pharmaceutics12070614 | |
| 942 | _cCF | ||