Few sentinel node (SN) studies in ovarian cancer have been reported, mainly because of the risk of tumor dissemination associated with the injection of tracers into the ovarian cortex. To our knowledge, the injection of tracers into the ovarian ligaments has not been explored. The aim of this study was to determine the feasibility of the SN procedure in ovarian cancer with tracer injection into the ovarian ligaments and to establish whether the procedure is safe for the healthcare workers. Methods: The study included patients who were at high risk of ovarian malignancy. Blue dye and radioactive colloid were injected into the proper ovarian ligament and suspensory ligament of the ovary. To measure professional radiation exposure, ring dose meters were worn by the surgeon, theater nurse, and pathologist during 3 procedures. Results: An SN procedure was performed in 21 patients, and at least 1 SN location was identified in all patients using the γ probe before retroperitoneal exploration. SNs were located in the paraaortic and paracaval regions only in 67% of the patients, in the pelvic region only in 9%, and in both the paraaortic/paracaval and the pelvic regions in 24%. All but 2 SNs were found on the ipsilateral side. In 6 patients who underwent retroperitoneal exploration, 1-4 SNs were identified using the γ probe and resected. Blue-stained SNs were detected in 2 patients. Positive SNs were detected in 1 patient with lymph node metastases. The amount of radiation exposure to the surgeon, theater nurse, and pathologist did not exceed the safe limit. Conclusion: The identification of SNs in all cases suggests that the SN procedure performed by injection of tracers in the ovarian ligaments is feasible and promising. The procedure is safe for the involved personnel. Further investigation is necessary to determine the clinical application of this new technique.

Tracer injection into ovarian ligaments has been shown to detect sentinel nodes (SNs) in patients with ovarian cancer. To determine the possibility that SNs are missed, this feasibility study compared their detection during surgery with their detection on postoperative SPECT/CT. Methods: In 8 patients (with either ovarian or endometrial cancer), after a staging lymphadenectomy including resection of SNs related to the ovary, SPECT/CT was performed within 24 h. Results: SPECT/CT identified hotspots in 4 patients at sites where SNs were resected. In 6 patients, additional sites were found, mainly in the pelvic region. Conclusion: Discrepancies between the g-probe and SPECT/CT may be due to missed SNs during surgery, but with respect to pelvic hotspots, in most cases they are more probably related to remnants of tracer at injection sites. With respect to sites where SNs were resected, remaining hotspots may have been caused by residual lymphatic flow after resection. In clinical early-stage epithelial ovarian cancer, the International Federation of Obstetrics and Gynaecology recommends a staging procedure that includes a complete pelvic and paraaortic lymphadenectomy (1). However, a complete lymphadenectomy is associated with morbidity, including nerve and vessel injury, increased blood loss, increased operating time, and the formation of lymph cysts and lymphedema (2-4). A sentinel node (SN) procedure may play an important role in the management of epithelial ovarian cancer. Few studies in patients with ovarian cancer have evaluated SNs, partly because of the risk of tumor dissemination associated with the injection of tracers into the ovarian cortex (5-9). In a previous pilot study, we avoided possible tumor cell spillage by injection of tracers into the ovarian ligaments rather than into the ovarian cortex (10). We identified at least one SN in all patients with suspected ovarian cancer (n 5 21) (11). However, by the nature of this approach without preoperative imaging of the SN locations, we were conscious that the single use of a g-probe or blue color to detect hotspots during surgery could lead to missed SNs. With this in mind, in the present feasibility study we describe patients in whom, after resection of SNs identified by g-probe and blue dye, postoperative SPECT/CT was performed. MATERIALS AND METHODS PatientsAs described previously, patients diagnosed with a pelvic mass suggestive of a malignant ovarian tumor, and patients with high-grade endometrial cancer planned for staging laparotomy, were eligible to participate in the study (10,11). We included both patients with suspected ovarian malignancy and patients with a high-grade uterine carcinoma. The latter group could be included because these patients undergo the same surgical procedure: total abdominal hysterectomy with bilateral salpingo-oophorectomy and a pelvic and paraaortic lymphadenectomy or lymph node sampling. All patients provided fully informed consent in writing before enrollment in the study, and the protocol was approved by the Local Eth...

Tumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [(68)Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing (68)Ga for preclinical CA IX imaging are scarce, and this is one of the first effective (68)Ga compounds reported for PET imaging of CA IX.

BackgroundCD13 is selectively upregulated in angiogenic active endothelium and can serve as a target for molecular imaging tracers to non-invasively visualise angiogenesis in vivo. Non-invasive determination of CD13 expression can potentially be used to monitor treatment response to pro-angiogenic drugs in ischemic heart disease. CD13 binds peptides and proteins through binding to tripeptide asparagine-glycine-arginine (NGR) amino acid residues.Previous studies using in vivo fluorescence microscopy and magnetic resonance imaging indicated that cNGR tripeptide-based tracers specifically bind to CD13 in angiogenic vasculature at the border zone of the infarcted myocardium.In this study, the CD13-binding characteristics of an 111In-labelled cyclic NGR peptide (cNGR) were determined. To increase sensitivity, we visualised 111In-DTPA-cNGR in combination with 99mTc-sestamibi using dual-isotope SPECT to localise CD13 expression in perfusion-deficient regions.MethodsMyocardial infarction (MI) was induced in Swiss mice by ligation of the left anterior descending coronary artery (LAD). 111In-DTPA-cNGR and 99mTc-sestamibi dual-isotope SPECT imaging was performed 7 days post-ligation in MI mice and in control mice. In addition, ex vivo SPECT imaging on excised hearts was performed, and biodistribution of 111In-DTPA-cNGR was determined using gamma counting. Binding specificity of 111In-DTPA-cNGR to angiogenic active endothelium was determined using the Matrigel model.ResultsLabelling yield of 111In-DTPA-cNGR was 95% to 98% and did not require further purification. In vivo, 111In-DTPA-cNGR imaging showed a rapid clearance from non-infarcted tissue and a urinary excretion of 82% of the injected dose (I.D.) 2 h after intravenous injection in the MI mice. Specific binding of 111In-DTPA-cNGR was confirmed in the Matrigel model and, moreover, binding was demonstrated in the infarcted myocardium and infarct border zone.ConclusionsOur newly designed and developed angiogenesis imaging probe 111In-DTPA-cNGR allows simultaneous imaging of CD13 expression and perfusion in the infarcted myocardium and the infarct border zone by dual-isotope micro-SPECT imaging.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0081-7) contains supplementary material, which is available to authorized users.

BackgroundThe concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments.Methods/DesignPatients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included.Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes.Trial registrationApproval number: NL40323.068.12Name: Medical Ethical Committee Maastricht University Hospital, University of MaastrichtAffiliation: Maastricht University HospitalBoard Chair Name: Medisch Ethische Commissie azM/UM