Near-infrared fluorescence imaging compared to standard sentinel lymph node detection with blue dye in patients with vulvar cancer – a randomized controlled trial

Objective. The aim of this study was to assess the superiority of ICG-99mTc-nanocolloid for the intraoperative visual detection of sentinel lymph nodes (SLNs) in vulvar squamous cell carcinoma (VSCC) patients compared to standard SLN detection using 99mTc-nanocolloid with blue dye. Methods. In this multicenter, randomized controlled trial, VSCC patients underwent either the standard SLN procedure or with the hybrid tracer ICG-99mTc-nanocolloid. The primary endpoint was the percentage of fluorescent SLNs compared to blue SLNs. Secondary endpoints were successful SLN procedures, surgical outcomes and postoperative complications. Results. Forty-eight patients were randomized to the standard (n = 24) or fluorescence imaging group (n = 24) using ICG-99mTc-nanocolloid. The percentage of blue SLNs was 65.3% compared to 92.5% fluorescent SLNs (p < 0.001). A successful SLN procedure was obtained in 92.1% of the groins in the standard group and 97.2% of the groins in the fluorescence imaging group (p = 0.33). Groups did not differ in surgical outcome, although more short-term postoperative complications were documented in the standard group (p = 0.041). Conclusions. Intraoperative visual detection of SLNs in patients with VSCC using ICG-99mTc-nanocolloid was superior compared to 99mTc-nanocolloid and blue dye. The rate of successful SLN procedures between both groups was not significantly different. Fluorescence imaging has potential to be used routinely in the SLN procedure in VSCC patients to facilitate the search by direct visualizatio

Optical imaging as an expansion of nuclear medicine : Cerenkov-based luminescence vs fluorescence-based luminescence

Integration of optical imaging technologies can further strengthen the field of radioguided surgery. Rather than using two separate chemical entities to achieve this extension, hybrid imaging agents can be used that contain both radionuclear and optical properties. Two types of such hybrid imaging agents are available: (1) hybrid imaging agents generated by Cerenkov luminescence imaging (CLI) of ß-emitters and (2) hybrid imaging agents that contain both a radioactive moiety and a fluorescent dye. One major challenge clinicians are now facing is to determine the potential value of these approaches. With this tutorial review we intend to clarify the differences between the two approaches and highlight the clinical potential of hybrid imaging during image-guided surgery applications

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

In the treatment of neuroendocrine tumors (NETs), complete surgical removal of malignancy is generally desirable, because it offers curative results. Preoperative guidance with radiolabeled somatostatin analogs, commonly used for NET diagnosis and preoperative planning, is limited by its low resolution, with the risk that tumor margins and small metastases will be incompletely resected with subsequent recurrence. A single hybrid probe combining radio-tracer and optical dye would enable high-resolution optical guidance, also during surgery. In the current study, the hybrid labeled somatostatin analog Cy5-DTPA-Tyr(3)-octreotate (DTPA is diethylene triamine pentaacetic acid) was synthesized and evaluated for its ability to specifically trace NET cells in vitro and in an animal model. The performance of the hybrid tracer was compared with that of octreotate with only radiolabel or only optical label. Methods: The binding affinity and internalization capacity of Cy5-DTPA-Tyr(3)-octreotate were assessed in vitro. Biodistribution profiles and both nuclear and optical in vivo imaging of Cy5-In-111 -DTPA-Tyr(3)-octreotate were performed in NET-bearing mice and compared with the performance of In-111-DTPA-Tyr(3)-octreotate. Results: In vitro studies showed a low receptor affinity and internalization rate for Cy5-DTPA-Tyr(3)-octreotate. The dissociation constant value was 387.7 +/- 97.9 nM for Cy5-DTPA-Tyr(3)-octreotate, whereas it was 120.5 +/- 18.1 nM for DTPA-Tyr(3)-octreotate. Similarly, receptor-mediated internalization reduced from 33.76% +/- 1.22% applied dose for DTPA-Tyr(3)-octreotate to 1.32% +/- 0.02% applied dose for Cy5-DTPA-Tyr(3)-octreotate. In contrast, in vivo and ex vivo studies revealed similar tumor uptake values of Cy5-In-111-DTPA-Tyr(3)-octreotate and In-111 -DTPA-Tyr(3)-octreotate (6.93 +/- 2.08 and 5.16 +/- 1.27, respectively). All organs except the kidneys showed low background radioactivity, with especially low activities in the liver, and high tumor-to-tissue ratios were achieved-both favorable for the tracer's toxicity profile. Hybrid imaging in mice confirmed that the nuclear and fluorescence signals colocalized. Conclusion: The correlation between findings with the optical and the nuclear probes underlines the potential of combining SPECT imaging with fluorescence guidance and shows the promise of this novel hybrid peptide for preoperative and intraoperative imaging of NET

EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases.

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings

From interventionist imaging to intraoperative guidance: New perspectives by combining advanced tools and navigation with radio-guided surgery.

The integration of medical imaging technologies into diagnostic and therapeutic approaches can pro-vide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonanceimaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computedtomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, someimaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound,gamma or optical imaging) where they provide the surgeon with real-time information during theprocedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasibletoday. With the development of new tracers and portable imaging devices, these advances will reinforcethe role of interventional molecular imaging.</p