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Unlabelled: Many patients referred for PET suffer from anxiety, possibly affecting the workflow and patient experience. In addition, patient anxiety may affect image quality through uptake of (18)F-FDG in muscles or brown adipose tissue (BAT).This study investigated the effects of a nonpharmacologic intervention-the use of audiovisual imagery in the PET uptake room-on patient anxiety and false-positive uptake of (18)F-FDG (in muscles and BAT). Methods: A 2-stage study was conducted on 101 patients. The cohort undergoing the intervention included 51 patients. The first stage (n = 35) included physiologic measurements (cardiovascular activity, muscular activity, skin conductance, and cortisol), a state anxiety questionnaire, and visual evaluation of (18)F-FDG uptake in muscles and BAT; the second stage (n = 66) included only the state anxiety questionnaire and the (18)F-FDG uptake evaluation. Results: Throughout the stay in the uptake room, a significant decrease in overall anxiety was found, together with several other significant changes in patient physiology. In the cohort with audiovisual intervention, however, the decrease in patient anxiety was significantly larger. The cohort with intervention also showed significantly lower (18)F-FDG uptake in BAT but not in muscles. Conclusion: The investigated audiovisual intervention helps to lower patient anxiety in the PET uptake room and can lower false-positive (18)F-FDG uptake in BAT. [ABSTRACT FROM AUTHOR]

Background: The current expansion of image-guided surgery is closely related to the role played by radio-guided surgery in supporting the sentinel node (SN) procedure during more than three decades. The so-called triple approach (lymphoscintigraphy, gamma probe detection and blue dye) was not only essential in the seminal validation of the SN procedure but also a first collective learning effort based on skill transfer and outcome-related evaluation which laid the fundaments to delineate the field of intraoperative molecular imaging (IMI) based on a similar multimodality approach and multidisciplinary practice., Methods: These elements are also becoming valid in the current incorporation of SPECT/CT and PET/CT to existing and new protocols of IMI procedures and SN mapping concerning other clinical applications. On the other hand, there is a growing tendency to combine novel modern technologies in an allied role with gamma guidance in the operating room following the development of hybrid tracers and multimodal detection approaches. Against this background, learning initiatives are required for professionals working in this area., Results: This objective has led to a group of European practitioners with large experience in SN mapping and IMI applications to give shape to a programme made up out of specific learning modules aimed to be used as a conductive thread in peripherical or centralised training instances concerning the topic., Conclusion: The presented work, written as a tutorial review, is placed in an available prior-art context and is primarily aimed at medical and paramedical practitioners as well as at hardware and software developers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view., Methods: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image-guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices., Results: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging., Conclusion: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach., (© 2024. The Author(s).)

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT 1-2 tumours without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumours, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18 F-FDG PET/CT in an effort to tailor systemic and loco regional treatment., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy., Methods: We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99m Tc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months., Results: Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P  = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P  = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge ( N  = 42) and BI-RADS 3 lesions ( N  = 113) MBI detected 7 of 8 occult malignancies., Conclusion: MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: In muscle-invasive bladder cancer (MIBC), lymph node invasion has proven to be an independent predictor of disease recurrence and cancer-specific survival. We evaluated the feasibility of targeting the sentinel node (SN) for biopsy in MIBC patients using the hybrid tracer indocyanine green (ICG)- 99m Tc-nanocolloid for simultaneous radioguidance and fluorescence guidance., Methods: Twenty histologically confirmed cN0M0 MIBC patients (mean age, 63.3 years; range, 30-82 years), scheduled for radical cystectomy with SN biopsy and extended pelvic lymph node dissection (ePLND), were prospectively included. Twelve patients were operated on following neoadjuvant chemotherapy. The patients received lymphoscintigraphy as well as SPECT/CT after 4 transurethral injections of ICG- 99m Tc-nanocolloid (mean, 208 MBq; range, 172-229 MBq) around the tumor/scar in the detrusor muscle of the bladder on the day before radical cystectomy. Sentinel node resection was performed under radioguidance and fluorescence guidance., Results: Nineteen patients could be analyzed. On preoperative imaging, SNs could be identified in 10 patients (53%; mean, 1.6 SN/patient), which revealed drainage pathways outside the ePLND in 20% of the patients. Interesting to note is that 2 patients (10%) with preoperative nonvisualization displayed fluorescent and radioactive SNs during surgery. Location of the primary tumor near the left lateral side of the bladder seemed to be a factor for nonvisualization. Nodal harvesting with ePLND varied among patients (mean, 23.3). Histopathology confirmed tumor-positive nodes in 4 (21%) of all patients. In the 2 patients where an SN could be identified, the ePLND specimens were tumor-negative. All patients with tumor-positive nodes had advanced disease (stage III)., Conclusion: Sentinel node biopsy in bladder cancer using the hybrid tracer ICG- 99m Tc-nanocolloid is feasible, and preoperative imaging is predictive for the ability to perform SN biopsy in 83% of the patients who displayed an SN. In patients with a successful preoperative SN mapping using lymphoscintigraphy and SPECT/CT, the intraoperative SN guidance and detection were effective, even outside the ePLND area. As such, this study underscores the critical role that preoperative imaging plays in challenging image-guided surgery applications., Competing Interests: Conflicts of interest and sources of funding: This work was partially supported by an NWO-STW-VIDI grant (grant STW BGT11272). There are no potential conflicts of interest or payments received from a third party., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Sentinel lymph node (SN) biopsy (SNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technologic refinements, including the introduction of SPECT/CT, as well as radioguidance and fluorescence guidance. The purpose of the current study was to evaluate the effect of this technologic evolution on SNB in the head and neck region. The primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN, and postoperative complications. Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided into 4 groups: 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a γ-ray detection probe and patent blue ( n = 30); 2006-2007, with addition of preoperative road maps based on SPECT/CT ( n = 15); 2008-2009, with intraoperative use of a portable γ-camera ( n = 40); and 2010-2016, with addition of near-infrared fluorescence guidance ( n = 192). Results: In total, 277 patients were included. At least 1 SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%): 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%), and 40 in group 4 (20.8%). Regional recurrences in patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (group 1, 16.7%; group 2, 0%; group 3, 14.3%; group 4, 11.1%). The number of harvested nodes increased with advancing technologies ( P = 0.003), whereas Breslow thickness and operation time per harvested SN decreased ( P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time, and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without an increase in overall operation time, possibly indicating an improved surgical efficiency. Operation time per harvested SN decreased; the average FN rate remained 11.9% and was unchanged over 23 y. There was no significant change in postoperative complication rate., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Recent technical advances and implementation of novel radiotracers have further increased the potential of radioguided surgery for a broad variety of malignancies. Indeed, the possibilities for future applications of novel radiotracers in diverse oncological strategies has become more promising than ever. This literature review aims to provide a contemporary update on a selected group of radiotracers and evaluates the usability of radioguided surgery and sentinel node procedures, focusing on most promising advances. For example, the impact of targeted radiotracers on prostate specific membrane antigen (PSMA), CD206 receptor-targeted agents ( 99m Tc-tilmanocept), and hybrid tracers adding fluorescence to radioguidance (ICG- 99m Tc-nanocolloid) as well as targeting hypoxia-induced carbonic anhydrase IX (CAIX) will be covered. Furthermore, future outlooks on the implementation of gold nanoparticles (AuNP's), but also technical advances in improved radiotracer detection by hybrid gamma devices will be discussed.

Introduction and Objectives: To evaluate the migration of 99m Tc-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration., Materials and Methods: For 29 primary tumours in 28 patients (mean age: 62y, range: 45-81y) scheduled for SN biopsy planar images were acquired 10 and 120min after administration of 74MBq 99m Tc-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT-CT was performed immediately after delayed planar images to enable anatomical lymph node localization., Results: SNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (N=29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2h compared to 15min decreased with an average of 66% (range: 15-96%). SN/non-SN 2h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3-15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%)., Conclusion: 99m Tc-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake. This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of 99m Tc-tilmanocept with standard SN radiotracers in larger series of patients is necessary., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

We review recent technological advances and new clinical indications for sentinel node (SN) and radioguided surgery in order to delineate future tendencies of interventional nuclear medicine in this field. A literature research was performed in PubMed to select relevant articles to be used as key references for analysis of the current approaches and tendencies in SN and radioguided surgery, as well as the evolving contribution of nuclear medicine intervention techniques to the various clinical applications. For classic indications such as melanoma and breast cancer, the incorporation of the SN approach based on the combined use of existing and new preoperative and intraoperative technologies in high-risk patient categories is becoming an emerging area of clinical indication. For SN biopsy staging in other malignancies with more complex lymphatic drainage, the incorporation of sophisticated tools is most helpful. The consecutive use of PET/CT and the SN procedure is increasing as a potential combined approach for the management of specific areas such as the axilla and the pelvis in patients at high risk of regional dissemination. Also, for the management of locoregional metastasis and oligometastatic disease, interventional nuclear medicine techniques are becoming valuable alternatives. The extended experience with SN biopsy is leading to technological advances facilitating the incorporation of this procedure to stage other malignancies with complex lymphatic drainage. New nuclear medicine-based approaches, incorporating SPECT/CT and PET/CT to guide resection of SNs and occult metastases, have recently been gaining ground.

Objective: The hybrid tracer indocyanine green (ICG)-Tc-nanocolloid has been introduced for sentinel node imaging. However, until now, a comparison of this tracer with other radiocolloids with a larger particle size has not been effectuated. Based on a head-to-head evaluation in patients with melanoma, we have compared ICG-Tc-nanocolloid (particle size 5-80 nm) with Tc-Senti-Scint (particle size 100-600 nm) to establish differences in drainage pattern and sentinel node localization using lymphoscintigraphy and single-photon emission computed tomography combined with computer tomography (SPECT-CT) in melanoma patients scheduled for sentinel node biopsy., Methods: Twenty-five patients (mean age: 56.9 years, range: 25-79 years) with a melanoma scheduled for SLN biopsy prior to (re)excision of the primary lesion (scar) were prospectively included following a two-day procedure. The first day, after Tc-Senti-Scint injection in four intradermal depots around the primary lesion or scar, early/delayed lymphoscintigraphy and SPECT-CT images were acquired. The injection sites were marked. The second day, after assessing lymph node radioactivity using planar scintigraphy, ICG-Tc-nanocolloid was injected at the previously marked skin points and imaging was performed. The paired planar and SPECT-CT images of both tracers were evaluated with respect to drainage patterns, SLN visualization and non-SLN appearing., Results: Twenty-four out of 25 patients were evaluable. SLN visualization on a patient basis was 100% for ICG-Tc-nanocolloid and 96% for Tc-Senti-Scint, whereas uptake in non-SLNs was found in, respectively, 71% (17/24) and 61% (14/23). Concordance in drainage to 45 lymph node basins was 91%. Discordant drainage was found for two melanomas in the head-and-neck and one in the clavicular area. Unique lymph node basins were seen in 44/45 (98%) for ICG-Tc-nanocolloid and 42/45 (93%) for Tc-Senti-Scint. Concerning identified SLNs, the number was similar for both tracers (n = 58); however, more non-SLNs (65 vs 50) were visualized with ICG-Tc-nanocolloid than with Tc-Senti-Scint., Conclusion: A slightly higher SLN visualization accompanied by a tendency to depict more non-SLNs was found for ICG-Tc-nanocolloid. Excepting the head and neck area, an overall high concordance in drainage was found for both radiotracers. With an additional value for the hybrid tracer due to the combination of preoperative imaging and the additional visual signal in the operation room, added by the fluorescent component of the hybrid tracer, there was a preference for ICG-Tc-nanocolloid.

Purpose: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts., Methods: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected., Results: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer., Conclusions: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine- 99m Tc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach.

Purpose: Diagnostic imaging modalities have moderate sensitivity for the identification of lymph node (LN) metastases in prostate cancer (PCa) patients. Mapping the lymphatic drainage from the prostate can help to identify the LNs directly draining from the tumour (sentinel nodes (SNs)); the LNs stated to have the highest chance of containing metastatic cancer cells. Although the lymphatic drainage may differ between segments within the prostate, the location of the primary tumour is not routinely taken into account during peripheral zone-aimed tracer administration. This study evaluates whether linking the SN procedure to the primary cancer deposits increases the identification accuracy of lymphatic metastases., Methods: Sixty-seven PCa patients, scheduled for robot-assisted laparoscopic prostatectomy (RALP) and extended lymph node dissection (ePLND) with subsequent SN biopsy, were included in this retrospective study. After injection of the hybrid tracer ICG- 99m Tc-nanocolloid in the prostate, SN mapping was performed based on lymphoscintigraphy and SPECT/CT. SNs were resected using a combination of radio- and fluorescence guidance. Pathology was used to determine the primary tumour location and metastatic spread. Fluorescence imaging of paraffin-embedded prostate tissue was used to determine the location of the tracer deposits in the prostate. This deposition was related to the primary tumour location, the lymphatic drainage pattern of the injected tracer, and the metastatic spread., Results: In total 265 radioactive LNs (211 SNs and 54 higher-echelon nodes in 64 patients; 4.3 LNs per patient; IQR: 2-6) were identified. In three patients (4%) preoperative imaging did not allow identification of SNs. Tumour-positive SN visualization within the pelvis was shown to be influenced by intraprostatic location of tracer administration. This could be concluded from (1) a clear correlation between lymphatic drainage to the right or left side of the body and tracer deposition on the right or left side of the prostate, (2) visualization of a higher number of LNs after dorsal tracer deposition compared with ventral tracer deposition, (3) different drainage patterns observed for tracer deposition into the base or apex of the prostate, and (4) the indication that intratumoural tracer deposition increases the chance of visualizing nodal metastases compared with extratumoural tracer deposition., Conclusions: The correlation between the location of the tracer deposits, the location of the primary tumour, and the visualization of the (tumour-positive) SNs indicated that placement of tracer deposits is of influence on the visualized lymphatic drainage pattern. This suggests that tracer injection near or into the primary tumour site is beneficial for the identification of metastatic spread.

This case highlights the use of lymphoscintigraphy with SPECT/CT in patients with previous chest and/or axillary surgery. A 67-year-old woman with a history of left breast carcinoma treated with lumpectomy and radiotherapy, and a second lumpectomy of the ipsilateral breast for a second breast carcinoma, underwent a lymphoscintigraphy for a new left breast lesion. Planar images visualized an alternative lymphatic drainage to the contralateral axilla and to the left paravertebral area. SPECT/CT confirmed sentinel nodes in both stations.

Purpose: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (freehandSPECT) for the identification of technetium-99m-hydroxydiphosphonate ( 99m Tc-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches., Material and Methods: In 20 consecutive patients referred for scintigraphy with 99m Tc-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed., Results: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) >1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets., Conclusion: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high-quality freehandSPECT images supported the future exploration navigation strategies, e.g. guided needle biopsies., (Copyright © 2019 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)- 99m Tc-nanocolloid generates temporary tattoolike markings at the site of administration, we studied the ability to apply this tracer for tumor margin demarcation combined with SN biopsy. Methods: Nineteen patients with clinical T1-T2 oral tongue tumors received the traditional superficial 3 or 4 deposits of ICG- 99m Tc-nanocolloid (0.1 mL each), and in 12 patients additional deposits were placed deeply using ultrasound guidance (total of 6; 0.07 mL each). SN mapping was performed using lymphoscintigraphy and SPECT/CT. Before and directly after tumor excision, fluorescence imaging was performed to monitor the tracer deposits in the patient (fluorescent deposits were not used to guide the surgical excision). At pathologic examination, primary tumor samples were studied in detail. Results: The number of tracer depositions did not induce a significant difference in the number of SNs visualized ( P = 0.836). Reproducible and deep tracer deposition proved to be challenging. The fluorescent nature of ICG- 99m Tc-nanocolloid supported in vivo and ex vivo identification of the tracer deposits surrounding the tumor. Pathologic examination indicated that in 66.7% (8/12), all fluorescence was observed within the resection margins. Conclusion: This study indicates that tumor margin demarcation combined with SN identification has potential but that some practical challenges need to be overcome if this technique is to mature as a surgical guidance concept. Future studies need to define whether the technology can improve the radical nature of the resections., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma., Methods: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference"., Conclusion: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

Background: Sentinel lymph node biopsy (SLNB) after intratumoral injection of 99m Tc labeled nanocolloid and imaging with scintigraphy and SPECT/CT in renal tumors is feasible. However, sentinel lymph node (SN) non-detection rate with scintigraphy and SPECT/CT is high. The aim of the study was to determine factors affecting non-visualization (NV) of SN imaging in renal tumors. Seventy-eight patients with cT1-3 renal tumors received intratumoral injection of 225 MBq 99m Tc-labeled nanocolloid 1 day before (partial) nephrectomy. Radiotracer injection was followed by anterioposterior and lateral scintigraphy in combination with SPECT/CT 20 min and 2-4 h after. Surgical treatment of the tumor with sentinel lymph node biopsy by aid of γ-probe and-camera was performed the next day. Scintigraphy and SPECT/CT images were evaluated and patient, tumor, and procedure characteristics were collected for 73 eligible patients used in uni- and multivariable analysis of a potential association with NV., Results: A total of 80 (mean 1.1, IQR 0-2, max 6) sentinel lymph nodes in 46 patients were detected with scintigraphy and SPECT/CT. Preoperative visualization rate and intraoperative detection rate was 63% [95% CI 50-73%] and 61% [95% CI 49-72%], respectively. In uni- and multivariable analysis, the only factor associated with non-visualization was age, showing higher odds of non-visualization with higher age., Conclusion: Our study demonstrated that non-visualization of SNs in renal tumors is relatively high and is associated with patient age. Furthermore, kidneys and also its tumors are highly vascularized which may cause a wash-out effect that could be identified with decreased kidney-liver ratios. However, in our data, the effect was statistically inconclusive. Further studies are needed to improve visualization and standardize the procedure of SLNB in renal tumors. The percentage of NV limits the use of SLNB for research and clinical purposes in renal cancer.

Sentinel lymph node (SLN) biopsy is now the standard of care for regional staging in several solid tumors. The interstitial administration of a radiotracer around the primary tumor provide the possibility to sequentially obtain images with a gamma camera and visualize lymphatic mapping and the SLN. There is, however, a large geographical variability in those radiotracers and nanocolloids ranging from 15-100nm which are most widely employed in Europe, while filtered and unfiltered 99m Tc-sulfur colloid (range 20-1000nm) is usually used in the USA with different drawbacks in its use. The new radiotracer 99m Tc-Tilmanocept, designed specifically for the identification of SLNs and recently becoming commercially available in USA and Europe, appears to have the potency to overcome the shortcomings described for the conventional radiotracers used until now for SLN biopsy and at the same time to transform current imaging paradigms. After delineating the challenges for the next generation of radiotracers, this paper discusses the properties of 99m Tc-Tilmanocept, its validation process for SLN biopsy and its emerging clinical applications in various malignancies., (Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To investigate the rate of occult SN metastases, oncological outcome, and association of recurrence with the pattern of lymphatic tumour drainage in RCC., Materials and Methods: A pooled RCC sub-group analysis was conducted of secondary endpoints from a published feasibility and a phase II prospective single-arm SN study to investigate oncological outcome. Patients with cT1-3 (<10 cm) cN0M0 RCC of any sub-type were enrolled. After intratumoural injection of Tc 99m nanocolloid, pre-operative imaging of SNs with SPECT/CT was followed by (partial) nephrectomy with SN and regional lymph node dissection using a γ-probe. The patients were followed with a risk-adapted surveillance programme. Endpoints of the studies were analysed using Cox proportional hazard models., Results: Sixty-six RCC patients were included. Two patients (3%, 95% CI =0.5-11%) had occult SN metastases and remained free of disease at 57 and 72 months. Ten patients (15%, 95% CI =7-26%) developed recurrences, and four (6%, 95% CI =2.3-14.5%) had died of disease at a median follow-up of 57 months (IQR =18-72 months). Occurrence of distant metachronous metastases were associated with tumour size (HR =1.39, p = 0.02), pT stage (HR =6.83, p < 0.01 for comparison T1 vs T3/4), Grade 3/4 (HR =8.38, p = 0.05 for comparison 1/2 vs 3/4) and interaortocaval sentinel lymph node location (HR =10.52, p = 0.03 for comparison yes vs no)., Conclusions: The rate of occult metastatic SN is low, but long disease-free survival (DFS) was observed in two patients with occult SN metastases. We hypothesize an interaortocaval lymphatic route in thoracic recurrences. Evaluation of the prognostic and therapeutic role of sentinel lymph node biopsy (SLNB) requires a clinical trial in high-risk RCC.

Purpose: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)- 99m Tc-nancolloid was evaluated in a large cohort of patients., Patients and Methods: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG- 99m Tc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR)., Results: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced., Conclusion: With ICG- 99m Tc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

This study investigates whether radiomic features derived from preoperative positron emission tomography (PET) images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included when they had a unifocal primary cancer of ≥ 2.6 cm in diameter, had received a preoperative 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (CT) scan followed by surgery and had at least six months of follow-up data. 18 F-FDG-PET images were analyzed by semi-automatically drawing on the primary tumor in each PET image, followed by the extraction of 83 radiomic features. Unique radiomic features were identified by principal component analysis (PCA), after which they were compared with histopathology using non-pairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan-Meier method. Results: Forty women were included. PCA revealed four unique radiomic features, which were not associated with histopathologic characteristics such as grading, depth of invasion, lymph-vascular space invasion and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran's I, a feature that identifies global spatial autocorrelation, was correlated with OS ( P = 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran's I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran's I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings., (Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern of renal tumors in vivo with single photon emission/computerized tomography after intratumor radiotracer injection., Materials and Methods: We performed a phase II, prospective, single arm study to investigate the distribution of sentinel nodes from renal tumors on single photon emission/computerized tomography. Patients with cT1-3 (less than 10 cm) cN0M0 renal tumors of any subtype were enrolled in analysis. After intratumor ultrasound guided injection of 0.4 ml 99m Tc-nanocolloid we performed preoperative imaging of sentinel nodes with lymphoscintigraphy and single photon emission/computerized tomography. Sentinel and locoregional nonsentinel nodes were resected with a γ probe combined with a mobile γ camera. The primary study end point was the location of sentinel nodes outside the locoregional retroperitoneal templates on single photon emission/computerized tomography. Using a Simon minimax 2-stage design to detect a 25% extralocoregional retroperitoneal template location of sentinel nodes on imaging at α = 0.05 and 80% power at least 40 patients with sentinel node imaging on single photon emission/computerized tomography were needed., Results: Of the 68 patients 40 underwent preoperative single photon emission/computerized tomography of sentinel nodes and were included in primary end point analysis. Lymphatic drainage outside the locoregional retroperitoneal templates was observed in 14 patients (35%). Eight patients (20%) had supradiaphragmatic sentinel nodes., Conclusions: Sentinel nodes from renal tumors were mainly located in the respective locoregional retroperitoneal templates. Simultaneous sentinel nodes were located outside the suggested lymph node dissection templates, including supradiaphragmatic sentinel nodes in more than a third of the patients., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the clinical utility of molecular breast imaging (MBI) in patients with proven invasive breast cancer scheduled for breast-conserving surgery (BCS)., Methods: Following approval by the institutional review board and written informed consent, records of patients with newly diagnosed breast cancer scheduled for BCS who had undergone MBI for local staging in the period from March 2012 till December 2014 were retrospectively reviewed., Results: A total of 287 women (aged 30-88 years) were evaluated. MBI showed T stage migration in 26 patients (9%), with frequent detection of in situ carcinoma around the tumor. Surgical management was adjusted in 14 of these patients (54%). In 17 of 287 patients (6%), MBI revealed 21 proven additional lesions in the ipsilateral, contralateral breast or both. In 18 of these additional foci (86%), detected in 15 patients, malignancy was found. Thirteen of these 15 patients had ipsilateral cancer and 2 patients bilateral malignancy. In total, MBI revealed a larger tumor extent, additional tumor foci or both in 40 patients (14%), leading to treatment adjustment in 25 patients (9%)., Conclusion: MBI seems to be a useful imaging modality with a high predictive value in revealing ipsilateral and bilateral disease not visualized by mammography and ultrasound. It may play an important role in delineating the extent of the index lesion during preoperative planning. Incorporation of MBI in the clinical work-up as an adjunct modality to mammography and ultrasound may lead to better selection of patients who could benefit from BCS.

Purpose: Recent developments in iterative image reconstruction enable absolute quantification of SPECT/CT studies by incorporating compensation for collimator-detector response, attenuation, and scatter as well as resolution recovery into the reconstruction process (Evolution; Q.Metrix package; GE Healthcare, Little Chalfont, UK). The aim of this experimental study is to assess its quantitative accuracy for potential clinical 99m Tc-sestamibi (MIBI)-related SPECT/CT application in neoadjuvant chemotherapy response studies in breast cancer., Methods: Two phantoms were filled with MIBI and acquired on a SPECT/CT gamma camera (Discovery 670 Pro; GE Healthcare), that is, a water cylinder and a NEMA body phantom containing six spheres that were filled with an activity concentration reflecting clinical MIBI uptake. Subsequently, volumes-of-interest (VOI) of each sphere were drawn (semi)automatically on SPECT using various isocontour methods or manually on CT. Finally, prone MIBI SPECT/CT scans were acquired 5 and 90 min p.i. in a locally advanced breast cancer patient., Results: Activity concentration in the four largest spheres converged after nine iterations of evolution. Depending on the count statistics, the accuracy of the reconstructed activity concentration varied between -4.7 and -0.16% (VOI covering the entire phantom) and from 6.9% to 10% (8.8 cm ⌀ cylinder VOI placed in the center of the phantom). Recovery coefficients of SUV max were 1.89 ± 0.18, 1.76 ± 0.17, 2.00 ± 0.38, 1.89 ± 0.35, and 0.90 ± 0.26 for spheres with 37, 28, 22, 17, and 13 mm ⌀, respectively. Recovery coefficients of SUV mean were 1.07 ± 0.06, 1.03 ± 0.09, 1.17 ± 0.21, 1.10 ± 0.20, and 0.52 ± 0.14 (42% isocontour); 1.10 ± 0.07, 1.02 ± 0.09, 1.13 ± 0.19, 1.06 ± 0.19, and 0.51 ± 0.13 (36% isocontour with local background correction); and 0.96, 1.09, 1.03, 1.03, and 0.29 (CT). Patient study results were concordant with the phantom validation., Conclusions: Absolute SPECT/CT quantification of breast studies using MIBI seems feasible (<17% deviation) when a 42% isocontour is used for delineation for tumors of at least 17 mm diameter. However, with tumor shrinkage, response evaluation should be handled with caution, especially when using SUV max ., (© 2018 American Association of Physicists in Medicine.)

Background: Interest in technetium-99m ( 99m Tc)-sestamibi imaging for neoadjuvant chemotherapy (NAC) response monitoring in locally advanced breast cancer (LABC) is increasing but remains matter of discussion. The present study conducted a meta-analysis of the diagnostic performance of 99m Tc-sestamibi to predict pathologic nonresponse to NAC for primary LABC., Materials and Methods: A systematic data search was performed. Studies with a minimum of 10 LABC patients that had evaluated 99m Tc-sestamibi imaging for NAC nonresponse using conventional planar scintimammography, breast-specific γ-imaging, and/or single photon emission computed tomography/computed tomography (SPECT/CT) were included. The histopathologic findings were the reference standard. The meta-analysis was performed using a mixed logistic regression model., Results: The search revealed 14 eligible studies with 529 patients. Of the 14 studies, 11 had evaluated scintimammography and 3 breast-specific γ-imaging. No studies examining SPECT or SPECT/CT were found. The overall estimated pooled sensitivity, specificity, and positive and negative likelihood ratios of 99m Tc-sestamibi imaging to predict nonresponsiveness to NAC were 70.3% (95% confidence interval [CI], 56.5%-81.3%%), 90.1% (95% CI, 77.5%-96.0%), 7.13 (95% CI, 3.08-16.53), and 0.33 (95% CI, 0.22-0.49), respectively. Only 3 studies (107 patients) evaluated 99m Tc-sestamibi imaging during NAC, reported an estimated pooled sensitivity of 87% (95% CI, 72%-100%) and specificity of 93% (95% CI, 85%-100%)., Conclusion: Only planar 99m Tc-sestamibi imaging has been investigated for NAC nonresponse in LABC but showed low sensitivity to predict pathologic nonresponse. However, most studies focused on the prediction of pathologic complete response after NAC. Although experience is limited, 99m Tc-sestamibi uptake during NAC seems highly sensitivity for the prediction of nonresponsiveness. Features such as SPECT/CT imaging, standardized quantification, relation to tumor subtypes, and proper timing have been insufficiently evaluated and require further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aimed to assess the value of dual-timepoint 18 F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18 F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18 F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18 F-FDG LN uptake relative to background. Semiquantitative analysis included SUV max and the corresponding retention index of SUV max , measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18 F-FDG PET/CT for an SUV max cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUV max cutoff of greater than 0. Conclusion: Standard 18 F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18 F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.

Background: The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false-negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET-CT before NST with those of the MARI procedure after NST, was analysed., Methods: A cohort of axillary node-positive patients was used to construct a hypothetical treatment algorithm based on a combination of PET-CT and the MARI procedure. In the algorithm, the number of fluorodeoxyglucose (FDG)-avid axillary lymph nodes (1-3 versus 4 or more) before NST and the tumour status of the MARI node (positive versus negative) after NST were used to tailor axillary treatment. All patients in the cohort underwent ALND, allowing estimation of potential overtreatment and undertreatment., Results: A total of 93 patients were included in the study. Between one and three FDG-avid axillary lymph nodes were observed in 59 patients, and four or more in 34 patients. The MARI node was tumour-negative in 32 patients and showed residual disease in 61. Treatment according to the constructed algorithm would have resulted in 74 per cent of patients avoiding an ALND, with potential undertreatment in three patients (3 per cent) and overtreatment in 16 (17 per cent)., Conclusion: Tailored axillary treatment after NST in node-positive patients, by combining PET-CT before NST and the MARI procedure after NST, has the potential for ALND to be avoided in 74 per cent of patients., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)