Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

Using a porcine model and ex vivo human prostate cancer specimens, a hybrid PSMA tracer (99mTc-EuK-(SO3)Cy5-mas3) administered at a microdosing regime enabled fluorescence-guided robot-assisted radical prostatectomy. In pigs, the prostate gland was visualized based on basal PSMA expression, and tracer half-lives in blood and urine were 85 and 390 minutes, respectively, suggesting an interval of over 7 hours between administration and surgery. Ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA immunohistochemistry, confirming tumor identification. The findings indicate that intraoperative PSMA-mediated fluorescence imaging with a microdosing approach is feasible and has translational potential.

Study at a glance

Abstract

Abstract Background With the rise of prostate-specific membrane antigen (PSMA) radioguided surgery, which is performed using a microdosing regime, demand for visual target confirmation via fluorescence guidance is growing. While proven very effective for radiotracers, microdosing approaches the detection limit for fluorescence imaging. Thus, utility will be highly dependent on the tracer performance, the sensitivity of the fluorescence camera used, and the degree of background signal. Using a porcine model the ability to perform robot-assisted radical prostatectomy under fluorescence guidance using the bimodal or rather hybrid PSMA tracer (99mTc-EuK-(SO3)Cy5-mas3) was studied, while employing the tracer in a microdosing regime. This was followed by ex vivo evaluation in surgical specimens obtained from prostate cancer patients. Results T50% blood and T50% urine were reached at 85 min and 390 min, in, respectively, blood and urine. Surgical fluorescence imaging allowed visualization of the prostate gland based on the basal PSMA-expression in porcine prostate. Together, in vivo visualization of the prostate and urinary excretion suggests at least an interval of > 7 h between tracer administration and surgery. Confocal microscopy of excised tissues confirmed tracer uptake in kidney and prostate, which was confirmed with PSMA IHC. No fluorescence was detected in other excised tissues. Tumor identification based on ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA IHC. Conclusion Intraoperative PSMA-mediated fluorescence imaging with a microdosing approach was shown to be feasible. Furthermore, EuK‐(SO3)Cy5‐mas3 allowed tumor identification in human prostate samples, underlining the translational potential of this novel tracer. Trial registration Approval for use of biological material for research purposes was provided by the Translational Research Board of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital (NKI-AvL) under reference IRBm19-273 (22/10/2019).