Search Results (36)

Background: Meta-analyses on the prevalence and significance of thyroid incidentalomas at PET (TIP) are available only about [¹⁸F]FDG. Focal TIP at [¹⁸F]FDG PET is not rare and may be malignant lesions in about one-third of cases. The aim of this study is to perform a meta-analysis on the prevalence and clinical significance of TIP using other PET radiotracers beyond [¹⁸F]FDG. Methods: A comprehensive literature search of studies about TIP was carried out using four different databases, screened until 31 December 2024. Only original articles about TIP using radiopharmaceuticals other than [¹⁸F]FDG were selected. A proportion meta-analysis on the prevalence and clinical significance of TIP was carried out on a patient-based analysis using a random-effects model. Results: 21 studies (29,409 patients) were included in the meta-analysis. PET was performed using radiolabeled somatostatin analogues (SSA) [n = 5], choline [n = 6], prostate-specific membrane antigen (PSMA) [n = 7], or fibroblast activation protein inhibitors (FAPI) [n = 3]. The uptake pattern of TIP was described as focal, diffuse, or mixed/heterogeneous. The pooled prevalence of TIP was 5.6% for SSA-PET, 6.1% for choline-PET, 4.2% for PSMA-PET, and 3.6% for FAPI-PET. The final diagnosis of TIP with a diffuse pattern was a benign condition or represented a physiological uptake. Conversely, TIP with focal or mixed/heterogeneous pattern may represent a benign condition in most cases, but even a malignant lesion in 6–10% of cases. Conclusions: As for [¹⁸F]FDG, TIP using other radiopharmaceuticals is not rare. Most of them are benign, but those with focal or heterogeneous uptake patterns may represent a malignant lesion in some cases (even if the risk of malignancy is lower compared to [¹⁸F]FDG PET), thus requiring further evaluation. Further studies are warranted to better clarify the clinical impact of TIP detection. Full article

Background/Objectives: To conduct a systematic review to evaluate the detection rates (DR) of the three FDA-approved PSMA-targeted radiopharmaceuticals in patients with recurrent prostate cancer. Methods: Two individuals systematically searched MEDLINE, ScienceDirect, and Cochrane Libraries (February 2025), and independently reviewed all results to identify studies reporting patient-level ⁶⁸Ga-PSMA-11, ¹⁸F-DCFPyL, or ¹⁸F-flotufolastat DR in ≥100 evaluable patients with recurrent prostate cancer. Sample-weighted means (SWM) of extracted DR were calculated. Results: Of 5059 published articles, 37 met our inclusion criteria, reporting data from 8843 patients undergoing ⁶⁸Ga-PSMA-11 (n = 27), ¹⁸F-DCFPyL (n = 8), or ¹⁸F-flotufolastat (n = 2) studies. Heterogeneity was noted across enrolled populations, particularly in prior treatments. ⁶⁸Ga-PSMA-11 studies recruited patients with marginally higher median PSA than ¹⁸F-DCFPyL or ¹⁸F-flotufolastat studies (median PSA ranged from 0.1 to 10.7, 0.2–2.5, and 0.6–1.1, respectively). Reported overall DR ranged from 25 to 91% for ⁶⁸Ga-PSMA-11, 49–86% for ¹⁸F-DCFPyL, and 73–83% for ¹⁸F-flotufolastat, with SWM of 71%, 66%, and 79%, respectively. Post-prostatectomy DR were reported in 18 articles, resulting in SWM DR of 58% for ⁶⁸Ga-PSMA-11 (n = 12), 55% for ¹⁸F-DCFPyL (n = 4), and 76% for ¹⁸F-flotufolastat (n = 2). Among post-radiotherapy patients, SWM were 87% for ⁶⁸Ga-PSMA-11 (n = 4), 90% for ¹⁸F-DCFPyL (n = 2), and 99% for ¹⁸F-flotufolastat (n = 1). SWM DR at PSA < 1 ng/mL were 53%, 42%, and 66% for ⁶⁸Ga-PSMA-11 (n = 13), ¹⁸F-DCFPyL (n = 5), and ¹⁸F-flotufolastat (n = 2), respectively. Conclusions: Considerable heterogeneity exists across populations in studies of diagnostic PET radiopharmaceuticals. Despite a paucity of ¹⁸F-DCFPyL and ¹⁸F-flotufolastat studies compared with ⁶⁸Ga-PSMA-11, the available data suggest that all three radiopharmaceuticals provide high overall DR in patients with biochemical recurrence of prostate cancer. Full article

Objectives: To explore the impact of different standard of truth (SoT) methodologies on efficacy endpoints traditionally used in clinical trials of diagnostic radiopharmaceuticals, using data from the SPOTLIGHT study (NCT04186845) in patients with recurrent prostate cancer. Methods: Data from patients with baseline prostate-specific antigen (PSA) ≤ 5 ng/mL, who underwent ¹⁸F-flotufolastat imaging and had data for SoT determination, were reviewed. Majority-read patient level endpoints (verified detection rate [VDR] and patient-level positive predictive value [PPV]), and region-level PPV (in the prostate/prostate bed, pelvic lymph nodes, and extrapelvic sites) according to on-study reads by three blinded readers, were stratified by the SoT methodology (histopathology; post-PET confirmatory imaging; baseline/historic conventional imaging) used by the independent Truth Panel to verify ¹⁸F-flotufolastat-avid lesions. Differences between SoT groups for each endpoint were compared using a chi-square test (statistically significant if p < 0.0167). Results: Our analysis included 297 patients (median baseline PSA = 0.8 ng/mL): 56% (n = 166) had post-PET confirmatory imaging, 26% (n = 78) had baseline/historic conventional imaging, and 18% (n = 53) had histopathological confirmation of ≥1 PET-positive lesion. For all endpoints assessed, the highest majority-read values were achieved with histopathology SoT. For histopathology versus baseline/historic conventional imaging, VDR (77%) was 3.6-fold higher (p < 0.0001), patient-level PPV (79%) was 2.2-fold higher (p < 0.0001), and region-level PPV (50%) was 3.7-fold higher in the prostate/prostate bed (p = 0.009); smaller increases were seen in majority-read PPV in the pelvic lymph nodes (77%; 1.5-fold) and other sites (75%; 1.3-fold), but these were not of statistical significance. Conclusions: These data illustrate how SoT methods can substantially impact efficacy endpoints traditionally used in clinical trials of diagnostic radiopharmaceuticals. Notably lower endpoint values are achieved with imaging SoT than with histopathology. Full article

Background: This systematic review was performed to investigate the potential diagnostic role of fibroblast activation protein (FAP)-targeted radiopharmaceuticals in hepatocarcinoma (HCC) and cholangiocarcinoma (CCA). Methods: Relevant studies published between 2019 and 2023 were selected by searching PubMed and Scopus. The following data were extracted: authors, radiopharmaceuticals, sample size, country and year of publication, study design, and main results. Selected studies were analyzed using a modified version of the Critical Appraisal Skills Programme (CASP). Results: A total of 15 papers were finally selected, where 5 (33%) were retrospective, and 10 (67%) were prospective, with an overall number of 331 involved patients. Most of the studies (14/15, 93%) employed the FAP inhibitor series (FAPI), while only one research study used cyclic peptides as FAP-binding motifs. Twelve papers (80%) compared these FAP-targeted radiopharmaceuticals with ¹⁸F-FDG. The other 3/15 (20%) were not comparative studies and used exclusively ⁶⁸Ga-FAPI-04. ⁶⁸Ga-FAPI-04 is the most used radiopharmaceutical in analyzed studies (11/15, 73%), while other tracers, including ¹⁸F-FAPI, ⁶⁸Ga-FAPI-46, and ⁶⁸Ga-FAP-2286, were used in the remaining ones. Conclusions: FAP-targeted radiopharmaceuticals have good diagnostic accuracy in HCC and CCA, with potential and promising theragnostic applications. Full article

This study aims to retrospectively assess the safety of [²²⁵Ac]Ac-PSMA-PRLT, both as monotherapy and in combination (TANDEM) with Lutetium-177, concerning tolerance after the radiopharmaceutical administration and long-term safety, its impact on salivary glands’ function, overall survival (OS), and follow-up duration. Between December 2020 and September 2024, 89 patients received a total of 151 cycles of [²²⁵Ac]Ac-PSMA-PRLT. Patients with at least one follow-up (n = 71) were included in the analysis to evaluate xerostomia, as well as long-term hematological, renal, and hepatic toxicities, graded according to CTCAE v5.0. The most common adverse event after the radiopharmaceutical administration was flare pain (n = 16). As of the time of analysis, 68 patients had passed away (76.4%; range of survival 5 days to 39 months, median 7 months), while 21 patients were still alive (23.6%; follow-up duration: 1–33 months). Severe (G3/G4) long-term adverse events were rare, with 15 cases of G3 anemia (21.1%), 6 cases of G3 leukocytopenia (8.4%), and 14 cases of G3/G4 thrombocytopenia (19.7%). Hematological toxicity was primarily associated with severe bone marrow involvement or prior chemotherapy. Additionally, one case of G3 nephrotoxicity (1.4%) and six cases of G3 hepatotoxicity (8.4%) were observed. Only nine patients (12.7%) reported de novo xerostomia (G1/G2). In conclusion, this study demonstrates that [²²⁵Ac]Ac-PSMA PRLT, both as monotherapy and combined with [¹⁷⁷Lu]Lu-PSMA as TANDEM PRLT, is generally safe in terms of both tolerance after the radiopharmaceutical administration and long-term toxicity. Full article

The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (^58mCo) and the Positron Emission Tomography-isotope cobalt-55 (⁵⁵Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co²⁺ and Co³⁺. With cobalt-57 (⁵⁷Co) serving as a surrogate radionuclide for ^55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [⁵⁷Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of ⁵⁷Co from the complex. In conclusion, [⁵⁷Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR. Full article

(1) Background: Targeted alpha therapy is an emerging field in nuclear medicine driven by two advantages: overcoming resistance in cancer-suffering patients to beta therapies and the practical application of lower activities of ²¹²Pb- and ²²⁵Ac-labelled peptides to achieve the same doses compared to beta therapy due to the highly cytotoxic nature of alpha particles. However, quality control of the ²¹²Pb/²²⁵Ac-radiopharmaceuticals remains a challenge due to the low activity levels used for therapy (100 kBq/kg) and the formation of several free daughter nuclides immediately after the formulation of patient doses; (2) Methods: The routine alpha detection on thin-layer chromatograms (TLC) of ²¹²Pb- and ²²⁵Ac-labelled peptides using a MiniScanPRO+ scanner combined with an alpha detector head was compared with detection using an AR-2000 scanner equipped with an open proportional counter tube. Measurement time, resolution and validity were compared for both scanners; (3) Results: For ²²⁵Ac, the quality control values of the radiochemical purity (RCP) were within the acceptance criteria 2 h after TLC development, regardless of when the TLC probe was taken. That is, if the TLC probe was taken 24 h after radiosynthesis, the true value of the RCP was not measured until 5 h after TLC development. For ²¹²Pb-labelled peptides, the probe sampling did not have a high impact on the value of the RCP for the MiniScanPRO+ and AR-2000. A difference was observed when measuring TLC with the AR-2000 in different modes; (4) Conclusions: The MiniScanPRO+ is fast, does not require additional equipment and can also measure the gamma spectrum, which may be important for some radiopharmaceutical production sites and regulatory authorities. The AR-2000 has a better signal-to-noise ratio, and this eliminates the need for additional waiting time after TLC development. Full article

Background: Parathyroid tumors are classified as parathyroid neuroendocrine neoplasia (NEN) by the IARC-WHO classification. These tumors can occur with NENs from other sites, which often require total-body [68Ga]-DOTA-peptides PET/CT. This study aimed to assess the utility of [68Ga]-DOTA-peptide PET/CT in imaging parathyroid NENs and to evaluate the underlying mechanisms. Methods: Fifty patients with primary hyperparathyroidism (PHPT) and parathyroid NENs histologically confirmed as parathyroid adenomas (PAs) were included. PET/CT with [68Ga]-DOTA-peptide was performed in 16 patients with localized PAs, including 10 with MEN1 syndrome. Somatostatin receptor types 2 and 5 (SST2 and SST5) staining was performed on PAs from 48 patients. Somatostatin analogs (SSA) were prescribed in four patients with MEN 1 syndrome and 1 with persistent acromegaly, all with PAs and PHPT. The therapy effects on calcium and parathyroid hormone (iPTH) were evaluated. Results: [68Ga]-DOTA-peptide PET/CT detected 20 PAs with high radiopharmaceutical uptake. SST2 expression was negative on PA cell membranes in all cases and positive on endothelium in 39 (81%) PAs. Membrane SST5 expression was positive in 25 (52%) PAs and endothelial was positive in 40 (83%). Serum calcium levels decreased in patients on SSA therapy, while iPTH did not. Conclusions: PET/CT with [68Ga]-DOTA-peptides can detect parathyroid NENs. The incidental detection of high [68Ga]-DOTA-peptide uptake in the parathyroid region during whole-body PET/CT may prompt biochemical evaluation for PHPT. We suggest that endothelial SST expression mediates high radiopharmaceutical uptake by PAs and that SSA treatment can reduce hypercalcemia in PHPT patients. Full article

Alpha particle-emitting radiopharmaceuticals are in high demand for use in targeted alpha therapy. Ac-225 is currently produced using Th-229, but its annual production remains low, approximately 63 GBq. Previously, we produced a large amount of Ac-225 via the (n,2n) reaction in fast reactors; however, it required repetitive irradiation. In this work, we investigated a method to produce Th-229 via the (3n,x) reaction through long-term irradiation using neutrons from Pressurized Water Reactors. As target nuclides, Ra-226, which is commonly used for Ac-225 production, and Th-230, which is not widely used but is abundant, were selected. The evaluation was conducted under mixed conditions of Th-230 and Th-232. Ra-226 and Th-230 produce Th-229 (T1/2 = 7920 years) after long-term neutron irradiation. Th-229, which has a long half-life, the α-decays to produce Ra-225, and the β-decays of Ra-225 to produce Ac-225. These processes are semi-permanent owing to the long half-life of Th-229. Further, an irradiation method that does not require major changes in the upper part of the PWR fuel assembly geometry was employed by replacing the plugging device attached to the control rod guide tube with a target pin. The PWR loaded with abundant natural thorium target and irradiated with thermal neutrons for as long as approximately 5 years can produce more than twice the current world supply of Ac-225 annually and permanently. Full article

A novel gas chromatography method was developed using automatic injections to identify and quantify the amount of residual solvents or analytes in samples of fluorine-18 and carbon-11 radiopharmaceuticals. This approach evaluates seven analytes in less than 5 versus 13 min of acquisition time. The method additionally includes a 3 min bakeout to aid in the removal and carry-over of higher-boiling impurities. Chromatographic parameters such as column temperature, hold time, column pressure, flow rate, and split ratios were adjusted and optimized to analyze radioactive drug samples containing analytes which include methanol, ethanol, acetone, acetonitrile, triethylamine, N,N-dimethylformamide, and dimethyl sulfoxide. The relative standard deviation for each solvent was determined to be no greater than 1.6%. The method limit of detection (LOD) and limit of quantification (LOQ) were between 0.053 and 0.163 and 0.000 (5.791 × 10⁻⁶) and 0.520 mg/mL, respectively. This GC technique, using flame ionization detection (FID), was validated and is currently employed for the routine quality control of all approved IND and RDRC PET radiopharmaceuticals at our center. Full article

The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [²¹³Bi]Bi/[²²⁵Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [⁹⁰Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule–catheter system. The activity used for radiolabeling was 2–2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG. Full article

Background: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. Results: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [¹⁸F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [⁶⁸Ga]Ga-FAPI-04, [⁶⁸Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. Conclusion: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [¹⁸F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting. Full article

Background: Cancer is one of the leading causes of morbidity and mortality in the world. Its growing incidence and prevalence, as well as the advances in diagnostic and treatment tools, motivate an open debate about the economic burden it may place on health systems and have raised concerns about access to this technological innovation. There is a lack of information on the detailed costs of pharmacological treatment of cancer in our health setting. In this context, it is necessary to know the use of drugs in cancer treatment in conditions of real clinical practice. A real-word, evidence-based retrospective cohort study was conducted at Vall d’Hebron University Hospital (VHUH), the largest hospital complex in Catalonia, Spain, in order to determine the use of drugs and the associated cost in real clinical practice for the treatment of solid tumors in adult patients attended at this institution over 10 years (2010–2019). Methods: This was a single-center retrospective cohort study of adult cancer patients attended in clinical practice at the Medical Oncology Department of VHUH between 1 January 2010 and 31 December 2019. Data of prescription, preparation, and cost of antineoplastic treatments were analyzed by pharmacological class (cytotoxic drugs, immunotherapy, targeted therapy, radiopharmaceuticals, and others), by antineoplastic agent, and by type of tumor. The number of patients and the pharmaceutical expenditure corresponding to all these subgroups were recorded. The cost per patient in each tumor location was also calculated. Results: The study population included 13,209 patients with an overall pharmaceutical antineoplastic expenditure of EUR 120,396,097, increasing from 7.67% in relation to the total HUVH pharmaceutical expenditure in 2010 to 12.82% in 2019. By pharmacological class, the specific weight of the cost of targeted therapy is relevant (75.22% of pharmaceutical antineoplastic expenditure, 21.3% of patients) compared to the group of conventional cytotoxics (17.25% of pharmaceutical antineoplastic expenditure, 76.37% of patients), while immunotherapy has represented the largest relative increase, from 5% in 2014 to 12% in 2019. Eight targeted therapy drugs represented 50% of the costs of the targeted therapy drug class (palbociclib, trastuzumab, pertuzumab, bevacizumab, nivolumab, cetuximab, pembrolizumab, and trastuzumab emtansine). Eleven tumor sites accounted for 90% of the expenditure in 71% of all patients. Breast cancer had the highest expenditure during the study period (EUR 34,332,210) and at each individual year. Melanoma showed the highest increase, with 9.7% of total pharmaceutical antineoplastic expenditure in 2019 (2% of patients), representing a paradigm of the rising costs of cancer treatment due to the incorporation of new high-cost therapies. The average annual cost per patient was highly variable depending on the pathology. There was a growing increase in costs per patient in most tumor locations, particularly in patients with melanoma (from EUR 1922 in 2010 to EUR 37,020 in 2019), prostate cancer (from EUR 2992 in 2010 to EUR 14,118 in 2019), and non-small cell lung cancer (from EUR 3545 in 2010 to EUR 8371 in 2019). The relevance of the difference in monthly cost per patient that has been identified for the different intrinsic subtypes in breast cancer patients during 2019 (HER2+ EUR 2661/month, Luminal EUR 881/month, Triple negative EUR 386/month) makes us consider suggesting differentiated reimbursement rates for certain clinical conditions. Finally, support treatment with antiemetic drugs, erythropoietin stimulating agents, granulocyte-colony stimulating factor (G-CSF), and bone resorption inhibitors has involved a cost of EUR 5,751,910, which represents 4.6% of the overall pharmacological cost of cancer treatment. Conclusion: This study provides detailed insights on the oncological pharmaceutical expenditure for the treatment for solid tumors in the VHUH, based on real cost information from our hospital practice and for all antineoplastic therapies and types of solid tumors. This type of information on all the different types of cancer can be useful to better understand the economic burden of the disease and can be decisive for allocating public resources and funds for research, especially in those areas where information is scarce and therefore where further studies are needed. The contribution to knowledge of the cost of oncology therapy is of great value due to its realism and scope. Full article

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003–0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis. Full article

Methylene Blue (MB) is combined with radiopharmaceutical for intraoperative sentinel lymph node (SLN) mapping, but its role during SLN extirpation has not been investigated yet in veterinary medicine. The aim of this study was to assess whether MB increased surgical detection of SLN beyond the use of intraoperative gamma-probe (IGP) alone in clinically node-negative dogs with mast cell tumors (MCTs) following the detection of sentinel lymphocentrums (SLCs) via preoperative planar lymphoscintigraphy. Dogs enrolled underwent MCT excision and SLC exploration guided by both MB and IGP. Data recorded for each SLN were staining (blue/non-blue), radioactivity (hot/non-hot), and histopathological status (HN0-1 vs. HN2-3). A total of 103 dogs bearing 80 cutaneous, 35 subcutaneous, and 1 mucocutaneous MCTs were included; 140 SLCs were explored, for a total of 196 SLNs removed. Associating MB with IGP raised the SLNs detection rate from 90% to 95%. A total of 44% of SLNs were metastatic: 86% were blue/hot, 7% were only blue, 5% were only hot, and 2% were non-blue/non-hot. All HN3 SLNs were hot. Combining MB with IGP can increase the rate of SLN detection in dogs with MCTs; nonetheless, all lymph nodes identified during dissection should be removed, as they might be unstained but metastatic. Full article