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000179273 041__ $$aEnglish
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000179273 1001_ $$0P:(DE-He78)584449af653618bdd9539e668604ad74$$aEder, Ann-Christin$$b0$$eFirst author
000179273 245__ $$aA New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer.
000179273 260__ $$aBasel$$bMDPI$$c2022
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000179273 520__ $$aThe development of PSMA-targeting low-molecular-weight hybrid molecules aims at advancing preoperative imaging and accurate intraoperative fluorescence guidance for improved diagnosis and therapy of prostate cancer. In hybrid probe design, the major challenge is the introduction of a bulky dye to peptidomimetic core structures without affecting tumor-targeting properties and pharmacokinetic profiles. This study developed a novel class of PSMA-targeting hybrid molecules based on the clinically established theranostic agent PSMA-617. The fluorescent dye-bearing candidates of the strategically designed molecule library were evaluated in in vitro assays based on their PSMA-binding affinity and internalization properties to identify the most favorable hybrid molecule composition for the installation of a bulky dye. The library's best candidate was realized with IRDye800CW providing the lead compound. Glu-urea-Lys-2-Nal-Chx-Lys(IRDye800CW)-DOTA (PSMA-927) was investigated in an in vivo proof-of-concept study, with compelling performance in organ distribution studies, PET/MRI and optical imaging, and with a strong PSMA-specific tumor uptake comparable to that of PSMA-617. This study provides valuable insights about the design of PSMA-targeting low-molecular-weight hybrid molecules, which enable further advances in the field of peptidomimetic hybrid molecule development.
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000179273 650_7 $$2Other$$aPSMA
000179273 650_7 $$2Other$$aguided surgery
000179273 650_7 $$2Other$$ahybrid molecules
000179273 650_7 $$2Other$$aprostate cancer
000179273 650_7 $$2Other$$atheranostics
000179273 7001_ $$aMatthias, Jessica$$b1
000179273 7001_ $$0P:(DE-He78)3373acf5d3b93adfd9ea973cf2d218aa$$aSchäfer, Martin$$b2
000179273 7001_ $$0P:(DE-He78)748cbc9500371079bf3d34fc41eb828c$$aGeberlein, Jana$$b3
000179273 7001_ $$0P:(DE-He78)b87fdbb732415b24f8c00a8e84109a35$$aSteinacker, Nils$$b4
000179273 7001_ $$0P:(DE-He78)033d979f00729281e709b85fe6cae972$$aBauder-Wüst, Ulrike$$b5
000179273 7001_ $$0P:(DE-He78)e979eb6b4ff6c757f9ff11cc320d5faa$$aDomogalla, Lisa-Charlotte$$b6
000179273 7001_ $$0P:(DE-He78)1a25bc9516a97a13551ebd083356d24f$$aRoscher, Mareike$$b7
000179273 7001_ $$0P:(DE-He78)13a0afba029f5f64dc18b25ef7499558$$aHaberkorn, Uwe$$b8
000179273 7001_ $$0P:(DE-He78)331382460d902d1341dc73db8b990f97$$aEder, Matthias$$b9
000179273 7001_ $$0P:(DE-He78)9793347ba83f527b81a22ab75af9378a$$aKopka, Klaus$$b10$$eLast author
000179273 773__ $$0PERI:(DE-600)2193542-7$$a10.3390/ph15030267$$gVol. 15, no. 3, p. 267 -$$n3$$p267$$tPharmaceuticals$$v15$$x1424-8247$$y2022
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