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.

Introduction: Radioguided surgery is an ever-evolving part of nuclear medicine. In fact, this nuclear medicine sub-discipline actively bridges non-invasive molecular imaging with surgical care. Next to relying on the availability of radio-and bimodal-tracers, the success of radioguided surgery is for a large part dependent on the imaging modalities and imaging concepts available for the surgical setting. With this review, we have aimed to provide a comprehensive update of the most recent advances in the field. Areas covered: We have made an attempt to cover all aspects of radioguided surgery: 1) the use of radioisotopes that emit γ, β + , and/or β − radiation, 2) hardware developments ranging from probes to 2D cameras and even the use of advanced 3D interventional imaging solutions, and 3) multiplexing solutions such as dual-isotope detection or combined radionuclear and optical detection. Expert opinion: Technical refinements in the field of radioguided surgery should continue to focus on supporting its implementation in the increasingly complex minimally invasive surgical setting, e.g. by accommodating robot-assisted laparoscopic surgery. In addition, hybrid concepts that integrate the use of radioisotopes with other image-guided surgery modalities such as fluorescence or ultrasound are likely to expand in the future.

Purpose Radioguided surgery has been widely used for clinical procedures such as sentinel node resections. In the (robotassisted) laparoscopic setting radioguidance is realized using laparoscopic gamma probes, which have limited maneuverability. To increase the rotational freedom, a tethered DROP-IN gamma probe was designed. Here we present the first in vivo feasibility study of this technology in prostate cancer patients. Methods Ten patients scheduled for a sentinel node procedure received four injections into the prostate with (indocyanine green-) 99mTechnetium-nanocolloid and underwent preoperative imaging (lymphoscintigraphy and SPECT/CT). The DROP-IN probe was inserted via the assistant port, still permitting the insertion and usage of additional laparoscopic tools. Results The sentinel nodes were resected using the da Vinci ® Si robot under guidance of DROP-IN gamma tracing and fluorescence imaging. The surgeon was able to independently maneuver the DROP-IN probe using the ProGrasp® forceps of the da Vinci® robot and distinguish sentinel nodes from background signal (such as the injection site). Conclusions Overall the DROP-IN design proves to be a valuable tool for robot-assisted radioguided surgery approaches.

With the introduction of the hybrid tracer indocyanine green (ICG)-99m Tc-nanocolloid, a direct relation between preoperative imaging and intraoperative fluorescence guidance was established. However, fluorescence guidance remains limited by its superficial nature. This study evaluated the feasibility of a nuclear medicinebased navigation concept that allowed intraoperative positioning of a fluorescence camera (FC) in the vicinity of preoperatively defined ICG-99m Tc-nanocolloid containing sentinel nodes (SNs). Methods: Five patients with penile cancer scheduled for SN biopsy were injected with ICG-99m Tc-nanocolloid followed by preoperative SPECT/CT imaging. The navigation device was used to provide a real-time augmented reality overlay of the SPECT/CT images and video output of the FC. This overlay was then used for FC navigation.

Biconcave thin water layers represent a template to induce organization of supramolecular structures into ordered monolayers. Here we show how micelles form extensive micrometer-sized pseudo-2D superstructures that reveal size-sorting and geometric pattern formation, as shown by cryo-transmission electron microscopy (cryoTEM). Electron-rich gold particles inside the micelles facilitate direct visualization and determination of size, composition, and ordering of the micellar assemblies over multiple length scales. Some of the patterns observed show intriguing geometric patterns for superstructures, including Fibonacci-like, double-spiral domains that also appear in, for example, sunflower seed head patterns.

With the rapid expansion of robot-assisted surgical procedures, the need for robot-compliant image guidance technologies has also increased. Examples hereof are the integrated firefly fluorescence camera, the drop-in ultrasound probe, and the recently introduced DROP-IN gamma probe. Combined with 68Ga–prostate-specific membrane antigen–(PSMA)–11 PET/CT (staging) and 99mTc-PSMA-I&S SPECT/CT (preoperative imaging), the latter DROP-IN gamma probe technology recently allowed us to perform the first clinical cases of robot-assisted PSMA-guided salvage surgery of lymphatic metastases.

The aim of the current narrative review was to summarize the available evidence in the literature on artificial intelligence (AI) methods that have been applied during robotic surgery. Methods A narrative review of the literature was performed on MEDLINE/Pubmed and Scopus database on the topics of artificial intelligence, autonomous surgery, machine learning, robotic surgery, and surgical navigation, focusing on articles published between January 2015 and June 2019. All available evidences were analyzed and summarized herein after an interactive peer-review process of the panel.

With the rise of fluorescence-guided surgery, it has become evident that different types of fluorescence signals can provide value in the surgical setting. Hereby a different range of targets have been pursued in a great variety of surgical indications. One of the future challenges lies in combining complementary fluorescent readouts during one and the same surgical procedure, so-called multi-wavelength fluorescence guidance. In this review we summarize the current clinical state-of-the-art in multi-wavelength fluorescence guidance, basic technical concepts, possible future extensions of existing clinical indications and impact that the technology can bring to clinical care.