Radioguided interventions and surgery: Interventional Nuclear Medicine

Abstract

Preoperative imaging of solid tumors is the cornerstone of adequate staging in cancer diagnosis. Patients with cN0 or preoperative staging imaging without lymph node involvement (iN0M0) may undergo curative surgery. In many solid tumors, the sentinel lymph node procedure (SN) helps to determine if micrometastatic lymph nodes are involved, leading to adequate staging and appropriate treatment choices.

During surgical procedures, the surgeon explores the operating field for target lesions of interest; both the primary tumor and the SN. In the bloodied operating field, small targets, such as the SN, are not always easy to find. Especially not in areas with difficult anatomy or richly vascularized and nerve-fed areas. Searching for this SN in these challenging areas can lead to unnecessary removal of healthy tissue with associated morbidities, incomplete resections (R1 resections), or a longer duration of surgery.

Accurate preoperative imaging, surgical planning, and intraoperative tools to guide the surgeon to the desired lesion can overcome these problems. Hybrid SN tracers have been shown to offer the best in both pre- and intraoperative lesion detection.Section 1 of this thesis focuses on clinical application with combined pre- and intraoperative imaging, using the hybrid SN-tracer ICG-99mTc-nanocolloid, alone or

in comparison to other radioactive tracers, for novel potential clinical indications. This section also focuses on 99mTc-Tilmanocept, a new generation SN tracer. Chapter 2 provides an overview of interventional nuclear medicine using existing and new tracers and different detection modalities that discuss the needs for and key indications of radioguided surgery (e.g., lymphatic mapping, creator delivery, and targeted tracer development) with respect to chemical and engineering initiatives. Chapters 3 and 4 compare other radiocolloids of different particle sizes with the hybrid tracer ICG-99mTc nanocolloid, which is based on the most widely used colloid particle size in Europe. In the clinical study, described in Chapter 3, lymphoscintigraphic drainage patterns, including SN and non-SLN of 99mTc-Senti-Scint and the standard tracer ICG-99mTc-nanocolloid, are compared in patients with melanoma of the head and neck and truck.In Chapter 4, drainage patterns, SN visualization and non-SN visualization of a relatively new kid on the block, 99mTc-Tilmanocept, a manose receptor binding tracer, are presented and discussed for SN procedures in patients with breast cancer and melanoma. Based on a prospective pilot study in patients with muscle-invasive bladder cancer, Chapter 5 describes the feasibility of SN targeting using the hybrid tracer indocyaninegreen (ICG)99mTc-nanocolloid for preoperative imaging and concomitant intraoperative radioconduction and fluorescence conduction. Section 2 describes innovations in the field of radioguided surgery. In a preclinical setting, Chapter 6 describes the sensitivity of using a freehand mobile SPECT gamma camera with 3D navigation to identify 99mTc-HDP positive lesions in bone scintigraphy. Furthermore, the possible use for future radioguided biopsy osseous and non-osseous applications is discussed. Chapter 7 describes the preclinical tracer development of a novel hybrid tracer for liver surgery. This approach is based on fluorescence-guided minimally invasive hepatobiliary surgery for liver cancer, including the use of preoperative imaging to visualize the lesions well in advance. Section 2 concludes with future perspectives in radioguided surgery as discussed in Chapter 8, which also contains additional suggestions for expanding the hybrid surgical guidance concept in robot-assisted surgery. In conclusion, radioguided surgery (RGS) has led to better preoperative surgical planning and a more personalized surgery approach for the patient. The development of tracers and instruments for the pre- as well as the intraoperative procedure has contributed to standardize SN biopsy, replacing extended lymph node dissections in numerous malignancies; this has led to significantly reduce complications such as nerve damage, bleeding, lymphedema and lymphatic leakage. RGS stands and falls with the proper use of tracer for both pre- and intraoperative purposes. Hybrid versions of the radiotracer shows the additional value of visual input during surgery besides the preoperative imaging and intraoperative radioguidance. Nowadays, some surgeons prefer the fluorescent SN procedure as single modality instead of the hybrid version. However, the use of fluorescence alone shows a trend of removing, in addition to the SN, a greater number of resected nodes than needs, drifting away from personalized surgery. In this context, the use of a hybrid approach with bimodal detection technology may solve the limitations of fluorescence alone. For the radioactive component the logistics is the same as used for radioguided surgery and additional investments in this regard are not necessary. Nevertheless, either resting on novel devices or original radiotracers gradual technological advances and subsequent clinical validations are necessary for continuous improving radioguided precision surgery in the future. The results described in this thesis demonstrate the added value of hybrid imaging in various indications and the potential of new hybrid tracers and medical devices in the operating room. Current expansion of use in other indications, development of targeted hybrid tracers and intra-operative devices will further increase the field of RGS and interventional Nuclear Imaging. The rise of IGR offers the field of IMI unique (out-of-the-box) growth capabilities. Not only in the traditional terms of (radio)pharmaceuticals, engineering, physics and expanding clinical indications, but also in terms of embracing up-and-coming digital-, performance-guided, and autonomous-surgery paradigms. Exploration of these opportunities will expand the impact that nuclear medicine and molecular imaging have on the future of patient care.