PSMA Theranostics Using PET and Subsequent Radioguided Surgery in Recurrent Prostate Cancer

Maurer, Tobias; Schwamborn, Kristina; Schottelius, Margret; Wester, Hans‐Jürgen; Schwaiger, Markus; Gschwend, Jürgen E.; Eiber, Matthias

doi:10.1016/j.clgc.2016.05.020

Cited by 19 publications

(10 citation statements)

References 23 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PSMA‐based PET imaging. In patients with advanced prostate cancer, it may also be used to enhance therapeutic effects of PSMA directed theranostics …”

Section: Introductionmentioning

confidence: 99%

Pharmacological upregulation of prostate‐specific membrane antigen (PSMA) expression in prostate cancer cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…PSMA‐based PET imaging. In patients with advanced prostate cancer, it may also be used to enhance therapeutic effects of PSMA directed theranostics …”

Section: Introductionmentioning

confidence: 99%

Pharmacological upregulation of prostate‐specific membrane antigen (PSMA) expression in prostate cancer cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Recently, the existing classic theranostic concept comprising diagnostic imaging and targeted radionuclide therapy has been expanded by the use of 111 In-PSMA-I&T (19) and 99m Tc-PSMA-I&S (for i maging and s urgery) (20) for PSMA-targeted radioguided surgery of soft-tissue metastases in oligometastatic recurrent prostate cancer (21–23). A practical disadvantage of relying on intraoperative radioguidance alone is the acoustic and numeric surgical guidance provided by γ-probes, which, although highly sensitive, have a limited spatial resolution.…”

mentioning

confidence: 99%

Synthesis and Preclinical Characterization of the PSMA-Targeted Hybrid Tracer PSMA-I&F for Nuclear and Fluorescence Imaging of Prostate Cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

The prostate-specific membrane antigen (PSMA)–targeted radiotracers 68Ga/177Lu-PSMA-I&T and 99mTc-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 natGa-/68Ga- and natLu/177Lu 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 natGa-/natLu-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 68Ga- and 177Lu-PSMA-I&F. In vivo, blood clearance of 68Ga- and 177Lu-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 68Ga-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, 68Ga/177Lu-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.

show abstract

“…Intraoperatively, however, the use of a conventional g-probe-similar to the ones used during sentinel node procedures (39)-allowed for accurate intraoperative detection of PSMA-positive lesions ( Fig. 4) that can be confirmed by autoradiographic studies (40). This concept was even compatible with the forward-thinking freehand SPECT technology (32).…”

Section: Noteworthymentioning

confidence: 99%

Prostate-Specific Membrane Antigen–Guided Surgery

et al. 2019

Self Cite

View full text Add to dashboard Cite

Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer.

show abstract

PSMA Theranostics Using PET and Subsequent Radioguided Surgery in Recurrent Prostate Cancer

Cited by 19 publications

References 23 publications

Pharmacological upregulation of prostate‐specific membrane antigen (PSMA) expression in prostate cancer cells

Pharmacological upregulation of prostate‐specific membrane antigen (PSMA) expression in prostate cancer cells

Synthesis and Preclinical Characterization of the PSMA-Targeted Hybrid Tracer PSMA-I&F for Nuclear and Fluorescence Imaging of Prostate Cancer

Prostate-Specific Membrane Antigen–Guided Surgery

Contact Info

Product

Resources

About