RT Journal Article
SR Electronic
T1 Preoperative PET/CT and fluorescence-guided surgery of prostate cancer with the PSMA-11-derived hybrid molecule PSMA-914: First clinical proof-of-concept
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1214
OP 1214
VO 62
IS supplement 1
A1 Eder, Ann-Christin
A1 Omrane, Mohamed
A1 Stadlbauer, Sven
A1 Roscher, Mareike
A1 Khoder, Wael
A1 Gratzke, Christian
A1 Kopka, Klaus
A1 Eder, Matthias
A1 Meyer, Philipp
A1 Jilg, Cordula
A1 Ruf, Juri
YR 2021
UL http://jnm.snmjournals.org/content/62/supplement_1/1214.abstract
AB 1214Introduction: Radical prostatectomy is an established standard curative treatment strategy for prostate cancer (PCa). One of the main challenges is the precise intraoperative localization and delineation of malignant tissue and potential metastases. Particularly robotic assisted surgery might benefit from guidance aided by targeted hybrid molecules featuring a radio- and fluorescent label. Here, we report the clinical proof-of-concept of preoperative PSMA-PET/CT imaging and subsequent fluorescence-guided surgery with the PSMA-11-derived peptidomimetic PSMA-targeting hybrid molecule Glu-urea-Lys-(HE)3-HBED-CC-IRDye800CW (PSMA-914). Methods: Up to now, two patients with high-risk PCa (Gleason Score 9) received preoperative PET/CT imaging 1 h and 2 h after intravenous injection of approximately 200 MBq 68Ga-PSMA-914, respectively. The day after PET imaging patients underwent fluorescence-guided daVinci-assisted radical prostatectomy with PSMA-914 administration 1 h prior to surgery. Intraoperative findings were verified by postoperative ex situ fluorescence analysis. This first-in-man proof-of-concept was performed as compassionate use in accordance with the ethical standards of the 1964 Helsinki declaration. Approval for data analysis and publication has been obtained from of the local ethics committee. Written informed consent for participation and publication was obtained from the patients. Results: Preoperative PET/CT imaging with 68Ga-PSMA-914 at 1 h revealed strong tracer uptake in primary tumor tissue in both patients (SUVmax 9.6 and 6.1 g/ml, respectively), slightly increasing until the 2 h measurement (10.9 and 6.6 g/ml, respectively). In one patient, parailiacal lymph node metastases were additionally found on PET imaging. During daVinci-assisted surgery, the specific fluorescence signal of PSMA-914 clearly visualized tumor tissue and resections were performed under fluorescence-guidance. Subsequent ex situ fluorescence detection confirmed tumor-specific enrichment of the hybrid molecule with a high contrast to surrounding healthy tissue. Conclusions: Our work demonstrates the first clinical translation of a peptidomimetic PSMA-targeting hybrid molecule. The successful first-in-man proof-of-concept with the novel PSMA-11-derived hybrid molecule PSMA-914 highlights the potential of this technology aiming at a precise pre- and intraoperative detection of PSMA-expressing malignancies. This novel approach is expected to significantly improve the personalized surgical treatment in prostate cancer patients.