Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
Postprint
DOI
PMC
 |
Open Access Gold (Paid Option) |
|
as soon as is submitted to ZB.
Synthesis and preclinical characterization of the PSMA-targeted hybrid tracer PSMA-I&F for nuclear and fluorescence imaging of prostate cancer.
J. Nucl. Med. 60, 71-78 (2018)
Publ. Version/Full Text
Postprint
DOI
PMC
The prostate-specific membrane antigen (PSMA)-targeted radiotracers Ga-68/Lu-177-PSMA-I&T and Tc-99m-PSMA-I&S (for imaging and surgery) are currently successfully used for clinical PET imaging, radionuclide therapy, and radioguided surgery of metastatic prostate cancer. To additionally exploit the high sensitivity and spatial resolution of fluorescence imaging for improved surgical guidance, a PSMA-I&T-based hybrid tracer, PSMA-I&F (DOTAGA-k(Sulfo-Cy5)-y-nal-k-Sub-KuE), has been developed and evaluated. Methods: The in vitro PSMA-targeting efficiency of PSMA-I&F, the reference PSMA-I&T, and their corresponding Ga-nat-/Ga-68- and Lu-nat/Lu-177 counterparts was determined in LNCaP cells via competitive binding assays (IC50) and dual-tracer radioligand and fluorescence internalization studies. Biodistribution and small-animal PET imaging studies were performed in CB17 SCID and LNCaP xenograft-bearing SHO mice, respectively, and complemented by intraoperative far-red fluorescence imaging using a clinical laparoscope. Additionally, fully automated serial cryosectioning and fluorescence imaging of 1 tumor-bearing animal as well as PSMA immunohistochemistry and fluorescence microscopy of organ cryosections (tumor, kidney, spleen) were also performed. Results: Compared with the parent PSMA-I&T analogs, the PSMA affinities of PSMA-I&F and its Ga-nat-/Lu-nat-complexes remained high and unaffected by dye conjugation (7.9 < IC50 < 10.5 nM for all ligands). The same was observed for the internalization of Ga-68- and Lu-177-PSMA-I&F. In vivo, blood clearance of Ga-68- and Lu-177-PSMA-I&F was only slightly delayed by high plasma protein binding (94%-95%), and very low accumulation in nontarget organs was observed already at 1 h after injection. Dynamic PET imaging confirmed PSMA-specific (as demonstrated by coinjection of 2-PMPA) uptake into the LNCaP xenograft (4.5% +/- 1.8 percentage injected dose per gram) and the kidneys (106% +/- 23 percentage injected dose per gram). Tumor-to-background ratios of 2.1, 5.2, 9.6, and 9.6 for blood, liver, intestines, and muscle, respectively, at 1 h after injection led to excellent imaging contrast in Ga-68-PSMA-I&F PET and in intraoperative fluorescence imaging. Furthermore, fluorescence imaging of tissue cryosections allowed high-resolution visualization of intraorgan PSMA-I&F distribution in vivo and its correlation with PSMA expression as determined by immunohistochemistry. Conclusion: Thus, with its high PSMA-targeting efficiency and favorable pharmacokinetic profile, Ga-68/Lu-177-PSMA-I&F serves as an excellent proof-of-concept compound for the general feasibility of PSMA-I&T-based hybrid imaging. The PSMA-I&T scaffold represents a versatile PSMA-targeted lead structure, allowing relatively straightforward adaptation to the different structural requirements of dedicated nuclear or hybrid imaging agents.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Psma ; Prostate Cancer ; Fluorescence ; Hybrid Tracer ; Intraoperative Guidance; Dual-modality; Guided Surgery; Radioguided Surgery; Surgical Guidance; Ligands; Agents; Therapy; Optimization; Radionuclide; Inhibitor
ISSN (print) / ISBN
0161-5505
e-ISSN
1535-5667
Journal
Journal of Nuclear Medicine
Quellenangaben
Volume: 60,
Issue: 1,
Pages: 71-78
Publisher
Society of Nuclear Medicine and Molecular Imaging
Publishing Place
1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Biological and Medical Imaging (IBMI)