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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.)

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.

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.

Background: Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery., Patients and Methods: Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds., Results: Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous., Conclusions: Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Purpose: To prospectively compare prone and supine acquired 18F-FDG PET/CT for visualization of primary tumors and regional lymph nodes in stage II/III breast cancer patients., Materials and Methods: One hundred ninety-eight patients were included consecutively from August 2010 to April 2012. One hour after administration of 180-240 MBq 18F-FDG, PET/CT images of the thorax were firstly acquired in prone position. Subsequently, a standard PET/CT in supine position from skull base to thighs was made. Both sets of images were tested in a univariate and a multivariate analysis for the number of lesions per breast or lymph node (LN) region and anatomical mismatch between PET and CT images., Results: Images in prone position showed less compression of breast tissue, more primary tumor (PT) multifocality (P < 0.001) and more avid axillary LNs (P < 0.001) compared with supine position. Anatomical mismatch of the axillary LN metastases was found more often on supine PET/CT images compared with prone (P = 0.004). Prone images showed a smaller PT functional volume compared with supine position (P < 0.001)., Conclusions: Prone position PET/CT improved the visualization of PT multifocality and the number of detected axillary lymph nodes. Therefore, it is a valuable addition to standard supine PET/CT in the protocol for locoregional assessment in stage II/III breast cancer patients.

Purpose: Although portable gamma cameras (PGCs) have been helpful to depict sentinel nodes (SNs), sometimes nuclear physicians or surgeons have difficulties to interpret PGC images because of the lack of anatomical information. The aim of the present study was to develop and clinically test the prototype of a new portable hybrid camera (PHC), which adds optical to γ-imaging., Methods: In 2 hospitals, the existing PGC (Sentinella S102; Oncovision) was upgraded with an optical module (BB2-08S2C-25; Point Grey Research) to build a PHC. Preoperative PHC overview images (positioned at 15 cm distance) and close-up image (position at <5 cm distance) were obtained from 25 patients (12 melanoma, 2 oral cavity, and 11 breast cancer) after conventional lymphoscintigraphy. Errors in the optical image coregistration were evaluated with a 5-mm accuracy for each patient., Results: Conventional lymphoscintigraphy and the close-up PHC images depicted 55 SNs in total. In the PHC overview images, the optical module offered fused optical and γ-imaging indicating the image field of view and anatomical SN locations. Average optical image coregistration errors were 1.0 cm (range, 0-2.0 cm)., Conclusions: Fused optical and γ-imaging with the prototype PHC is technically feasible and helpful for the image interpretation. The optical image visualizes the γ-image field of view, enabling SN localization in an anatomical context in a preoperative setting; however, for the operating room, the use of its optical component needs to be additionally adjusted.

Purpose: Freehand single-photon emission computed tomography (SPECT) (fh-SPECT) for optical tracked 3-dimensional radioactivity mapping raises popularity for sentinel node biopsy and other radio-guided procedures. However, the device seems to be complex, requiring both training and a standardized scan protocol. Therefore, the aim of this study was to compare handling reproducibility between novice and expert users; subsequently, using additional scans, we evaluated a standardized scan protocol to be tested in novice users after receiving training., Materials and Methods: Three groups (untrained novices, experts, and trained novices), each one composed of 5 fh-SPECT users, were given the same short introduction and the assignment to perform 3 fh-SPECT scans with the same time per scan. For the scans, a reproducible phantom with an iodine-125 point source was used. Furthermore, we performed probe-trajectory evaluation including pattern, speed, and length of scans based on recorded videos and digital target tracking., Results: The training period encompasses 30 minutes per novice user. The mean error in 3 directions based on 45 measurements was 7.4 mm for untrained novices and 3.2 mm for expert users. The trained novice group had a mean error of 2.9 mm (a significant 61% reduction), comparable to the expert group. The reproducibility values, expressed in SD, were 4.1 mm for the untrained novice group, 1.3 mm for the expert group, and 1.1 mm for the trained novices (73% improvement). The standardized scan protocol was demonstrated by means of trajectory evaluation, a scan path better systematized., Conclusion: Scanning with fh-SPECT for radio-guided surgery requires a specific training period to increase handling and reproducibility of 3-dimensional imaging, and to enhance its accuracy in the operating room.

The lymphatic drainage of cutaneous melanomas located on the upper trunk is often complex and sometimes follows an unexpected pattern. Occasionally, even direct drainage to cervical lymph nodes is seen. In this case series, 3 patients with lymphatic drainage to the neck derived from melanomas located over the manubrium sterni are described. There appears to be a restricted area that involves the manubrium sterni from which lymphatic drainage to different cervical node basins appears more frequent. SPECT/CT was helpful in visualizing these patterns and for the localization of the sentinel nodes.

An unusual sentinel node location in a patient with penile carcinoma is described. The preoperative lymphoscintigram showed a prepubic sentinel node. The node could be harvested during surgery. This case illustrates one of the advantages of lymphatic mapping in penile carcinoma: preoperative lymphoscintigraphy can identify lymph nodes outside the usual nodal basins.

A 1.5-cm nonpalpable mass was detected in the upper outer quadrant of the left breast by screening mammography in a 55-year-old woman. The patient was scheduled for a sentinel node procedure, and lymphoscintigraphy was performed the day before surgery. Unintentionally, she received an intraparenchymal tracer injection 3 cm away from the malignant lesion instead of the intended intratumoral injection. Lymphoscintigraphy revealed two sentinel nodes in the axilla. A second dose of Tc-99m nanocolloid was injected the next day into the primary tumor through a catheter that had been inserted under ultrasound guidance the previous day. Once more, a lymphoscintigraphic image was obtained that showed additional sentinel nodes in two different regions outside the axilla. This observation supports the authors' contention that lymphatic watersheds exist in the breast and highlights the importance of tracer administration into or close to the tumor.

The particular use of lymphoscintigraphy to document retention and drainage in cystic lymphangioma of the neck is reported. Radionuclide examination using Tc-99m colliod particles, performed before sclerosing treatment with tetracycline in a patient with a large lymphangioma located in the neck, demonstrated a satisfactory tumor retention and slow outflow, enabling the administration of tetracycline without (risk of) organ toxicity. The treatment was successfully performed.

Bone scintigraphy is very sensitive in detecting metastases in an early stage, when changes in osteoblast function precede morphologic changes. In many oncologic situations, however, osteoarticular abnormal changes seen on the bone scan are not caused by tumor infiltration. They may be due to tumor associated conditions, such as carcinoma polyarthritis and hypertrophic pulmonary osteoarthropathy. They also may be due to therapy-associated conditions, such as the flare effect on metastases due to hormonal treatment, chemotherapy or radiotherapy, and osteonecrosis as a complication of radiotherapy or the use of corticosteroids. The introduction of Colony Stimulating Factors (CSF) to reduce myelotoxicity have allowed higher doses of chemotherapeutic agents to be administered. Currently, there is research being performed on the clinical effects of CSF in phase-II studies. In addition to the flare response of metastases, increased uptake in the axial skeleton and/or juxta-articular areas on bone scintigraphy in five patients receiving CSF has been observed. This new phenomenon could be explained by a reaction to a very cellular marrow caused by the use of CSF. The clinical relevance of this finding remains to be established. The authors present an overview of these old and new phenomena seen on the bone scan with clinical and roentgenologic correlation.

In six patients with doxorubicin-related cardiotoxicity, the severity of decrease in left ventricle ejection fraction (LVEF) was associated with faster myocardial I-123 MIBG washout rates. In four patients with severely decreased LVEF (range 19% to 28%), the 4-hour washout rate varied from 43% to 56%. In two patients with moderate cardiotoxicity (LVEF 42% and 43%), the washout rates were 37% and 35%, respectively. In contrast, in another patient thought to have initial left ventricular dysfunction (LVEF dropped from 66% to 54%), the myocardial I-123 MIBG retention rate was not reduced (6% washout). Subsequent continuation of chemotherapy in this patient was without complication. Reduced I-123 MIBG uptake in the left ventricle generally correlated with areas with abnormal Fourier amplitude values, but in one of the patients with moderate cardiotoxicity, the I-123 MIBG uptake was not reduced in a region with loss of amplitude, indicating dysfunction but probably no myocardial denervation. Analysis of the regional myocardial retention in patients with cardiotoxicity showed no significant difference in the I-123 MIBG washout rates of both segments with or without loss of amplitude. These data suggest that in spite of a localized loss of ventricular function demonstrated by radionuclide angiocardiography, doxorubicin-related cardiotoxicity appears to be based on a global process of myocardial adrenergic derangement.