Human Serum Albumin Microspheres Research Articles

Биораспределение микросфер альбумина, меченных Re-188, при различных путях введения

Nowadays the radiolabeled microspheres are established tools for radioembolization of primary and metastatic liver cancer. Human serum albumin microspheres (HSA) are unique carriers for selective and controlled radionuclide delivery to malignant tumors. Rhenium-188 (Re-188), which decays with beta particles (2.12 MeV (71.1%) and 1.965 MeV (25.6%) and gamma emission (155 keV (15.1%)) is one of the most available and promising generator-based radionuclide for cancer therapy. The purpose of this work was to study the biodistribution of microspheres based on hu-man serum albumin labeled with Re-188 (Re-188-HSA) in animals after different routes of admin-istration. The size of more than 95% of microspheres was 10-20 μm. The studies were carried out on outbred white mice and inbred C57BL/6 mice with transplanted Lewis adenocarcinoma after intravenous, intramuscular and intratumoral administration. After intravenous injection the high-est amount of Re-188-HSA in organs and tissues was observed: up to 311.3%/g in lungs, up to 74.30%/g in thyroid gland, up to 12.70%/g in liver, up to 0,81%/g in blood. After the intramuscular injection of 188Re-HSA, the concentration of 188Re-HSA in organs and tissues was significantly lower and did not exceed 1%/g, except for thyroid gland (1,10-17.80%/g). After intratumoral injec-tion the amount of Re-188-HSA in tumor varied from 16.7 to 26.8%/g, that was higher as compared with other organs and tissues. Thus, the routes of Re-188-HSA administration significantly affect its behavior in the body. The obtained results can be used to evaluate the Re-188-HSA potential for radionuclide tumor therapy after intravascular or intratumoral administration.

Radioguided Surgery, a Cost-Effective Strategy for Treating Solitary Pulmonary Nodules: 20-Year Experience of a Single Center

IntroductionSurgical resection with minimally invasive approach is the gold standard for both definitive diagnosis and treatment of solitary pulmonary nodules (SPNs); however, it can be difficult to pinpoint small, deep, or subsolid nodes without palpating lung parenchyma. The primary endpoint of this study is showing that radioguided surgery is a cost-effective strategy to improve the effectiveness of video-thoracoscopic localization/resection of SPNs/ground-glass opacities (GGOs). Secondary endpoints are analyzing the morbidity of this technique and tips and tricks to better manage this method. MethodsSPN smaller than 20 mm and/or with a distance from the visceral pleura ≥5 mm underwent minimally invasive resection after computed tomography-guided injection of a solution composed of 0.1/0.2 mL of 99Tc-labeled human serum albumin microspheres and 0.1 mL of nonionic contrast. In the operating theater, a collimated probe connected to a gamma ray detector allowed localization of the target area. ResultsBetween 1997 and 2018, a total of 451 patients with SPN/GGO underwent minimally invasive surgery with a radioguided technique at our hospital. The mean SPN diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-29 mm). The mean time to a localizing nodule was 3 minutes (range, 1-5 minutes). No significant injection-related complications were reported; only 3.3% of patients (15 of 451) developed pneumothorax. Both 30- to 60-day and 90-day mortality were 0%. The rate of postoperative complications was 2.53% (prolonged air leak). The conversion rate to thoracotomy was 1.55% (7 of 451). ConclusionsOur 20-year experience shows that radioguided thoracoscopic surgery is a safe and feasible strategy to treat suspicious SPN/GGO, with a success rate of 98%.

Treatment of pulmonary nodule: from VATS to RATS.

The incidental detection of solitary pulmonary nodule (SPN) is currently increasing due to the widespread use of computed tomography (CT) during the follow up in oncological patients or in screening trials. A quick and definitive histological diagnosis of these nodes is mandatory as, in case of primitive lung cancer, an early detection could improve both surgical results and prognosis. The minimally invasive pulmonary resection (MIPR) is the gold standard procedure for diagnosis and treatment of small lung nodules, but it can be difficult to localize deep nonpalpable nodes that lie in the lung parenchyma. Hence, throughout the years several techniques have been developed to better localize deep or sub solid nodes. We describe our experience with radio-guided technique. Patients with SPN smaller than 10 mm and/or with a distance from the visceral pleura equal or larger than 10 mm underwent MIPR after CT injection of a solution containing 0.2 mL 99Tc-labelled human serum albumin microspheres and 0.1 mL of non-ionic contrast. During surgical procedures, a collimated probe, connected to a gamma-ray detector, was used to scan the lung and detect the target area. The area of major radioactivity was then resected. Between 2010 and 2015, 175 patients (M/F: 97/78) underwent minimally invasive resection (thoracoscopic or robotic) with radio-guided technique. The mean node diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-39 mm). No significant CT-guided-injection-related complications occurred, except for 13 patients (7.4%) who developed a pneumothorax (PNX) not requiring chest tube insertion. This technique guaranteed a successfully intra-operative node localization in 100% of cases. The mean duration of the surgical procedure was 44 min (range, 25-130 min). The mean length of pleural drainage and mean hospital stay was 2.6 days (range, 1-5 days) and 3.9 days (range, 1-7 days) respectively. No mortality or perioperative complications occurred. Pathology reports showed 105 metastases, 55 primitive lung cancers and 15 benign lesions. In case of suspicion of primitive lung tumour an intraoperative frozen exam was conducted, and all patients underwent lobectomy or segmentectomy with lymphadenectomy [41 patients with thoracotomy, 11 with robotic surgery and 3 with video-assisted thoracoscopic surgery (VATS)]. Our experience confirms that radio-guided thoracoscopic surgery (RGTS) is a feasible and safe procedure, thanks to its high success rate the radio-guided technique is helpful to overcome the lack of tactile feedback during MIPR [VATS and robotic-assisted thoracoscopic surgery (RATS)] and to limit conversion to open surgery.

Therapy of malignant ascites in vivo by 211At-labelled microspheres

Determination of the biological effect of the alpha emitter (211)At on cellular level as well as the assessment of dosimetric data in a tumour model in vivo. Transplantation of malignant ascitic cells in mice intraperitoneally and estimation of tumour characteristics (doubling time of the cells, mean survival of the animals following an i.p. application of a defined tumour cell number). (211)At labelled human serum albumin microspheres B-20 (MSP) of varying activity were injected into tumour bearing mice intraperitoneally. The effectiveness of the therapy was evaluated by means of determination of the duration of cell cycle arrest as well as the microscopic analysis of the rate of abnormal mitotic cells due to radiation induced damage. Furthermore, dose dependence of survival was evaluated. Three days following the intraperitoneally application of 8 x 10(6) tumour cells, 50-600 kBq (211)At-MSP were applied into the abdominal cavity. Considering the volume of ascites at this time and the administered activity, dose calculations were performed. An activity of 50 kBq caused a dose of 0.84 Gy. The increase of radiation induced effect on ascitic tumour cells was correlated with the dose. Between the duration of the cell cycle arrest and the administered activity, a directly proportional correlation was found. The mean survival of non-treated animals was 16.9 +/- 3.7 days. The prolongation of the survival was proportional to the activity administered. Using a dosage of 10 Gy, five animals out of 16 survived. Therapy of malignant ascitic cells using (211)At-MSP was effective in vivo. For tumour therapy, the (211)At represents a highly effective alternative to usually applied beta emitters.

Radiopharmaceutical development based on human blood albumin microspheres and 90Y

New radiopharmaceutial (RP) based on human serum albumin microspheres (MSA) and 90Y was developed for treatment of liver cancer. The optimized synthesis using chelation resulted in approximately 80% yield with high specific activity. The RP developed was tested in mice with inoculated sarcoma-37. In two weeks the tumor size reduced by 43% after the treatment with the dose of 500 μCi injected into the tumor site.

Preparation and imaging of rhenium-188 labeled human serum albumin microsphere in orthotopic hepatoma rats

ObjectiveThe present study relates to a method for preparing 188Re-labeled human serum albumin microspheres (HSAM) by 188Re(I)-tricarbonyl ion(188Re(OH2)3(CO)3)+). This radioactive particle can be subjected to radioembolization for liver tumor. MethodsThe particle sizes and conformations of HSA microspheres were analyzed by Particle sizes-Malvern mastersizer and Scanning Electron Microscope (SEM). For preparing 188Re(I)-tricarbonyl ion, the 188ReO4- was eluted from a 188W/188Re generator with saline. The radio labeling efficiency was analyzed with high-performance liquid chromatography (HPLC). Amino borane-reduced 188ReO4-was interacted with carbon oxide to form (188Re(OH2)3(CO)3]+). For preparing 188Re-HSA microspheres, the 188Re(I)-tricarbonyl ion was added into a vial with HSA microspheres. The in vitro stability was investigated. The rat was injected with 188Re-HSA microspheres via hepatic artery route. Nano-SPECT/CT Imaging was acquired after injection of 188Re-HSA microspheres. ResultsThe shape of HSA microsphere was rough surfaced sphere or oval-shaped. The particle size was distributed between 20 and 35μm. In the RP-HPLC-UV chromatography, the yield of 188Re(I)-tricarbonyl ion was 75–80%. The labeling efficiency of 188Re-HSA microspheres in this method was more than 85%. After incubation, the 188Re(I)-tricarbonyl ion labeled HSA microspheres were found to be stable in vitro in normal saline and rat plasma. The result of Nano-SPECT/CT Imaging quantification analysis indicated that the percentage of injection dose %ID was maintained at 95% ID-88% ID from 2 to 72h after injection with 188Re- HSA microspheres. ConclusionsThe method of 188Re(I)-tricarbonyl ion labeled HSA microspheres can proceed with high labeling yield. Furthermore, this method provided a convenient method for radio-labeling of HSA microspheres with 188Re as well as a kit for manufacturing.

Selective internal radiation therapy of hepatic tumours: Is coiling of the gastroduodenal artery always beneficial?

To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC). Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres ((99m)Tc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent (99m)Tc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed. The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients' clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n = 21) or in the periphery of the hepatic arteries (n = 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe (90)Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned. Coil embolization of the GDA may induce arterial hepato-intestinal collaterals. Although most of these collaterals do not impede (90)Y administration, SIRT may become unfeasible in specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver approach with coiling of the GDA is recommended.

Radio-guided thoracoscopic surgery (RGTS) of small pulmonary nodules

The demand for adequate tissue sampling to determine individual tumor behavior is increasing the number of lung nodule resections, even when the diagnosis is already recognized. Video-assisted thoracic surgery (VATS) is the procedure of choice for diagnosis and treatment of small pulmonary nodules. Difficulties in localizing smaller and deeper nodules have been approached with different techniques. Herein we report our 13-years' experience with radio-guided thoracoscopic resection. Patients with pulmonary nodules smaller than 1 cm and/or deeper than 1 cm, below the visceral pleura, underwent computed tomography (CT)-guided injection of a solution, composed of 0.2 ml (99)Tc-labeled human serum albumin microspheres and 0.1 ml nonionic contrast, into the nodule. During the VATS procedure, an 11-mm-diameter collimated probe connected to a gamma ray detector was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. From 1997 to 2009, 573 patients underwent thoracoscopic resection of small pulmonary nodules, 211 with the radio-guided technique. There were 159 men and 52 women, with an average age of 60.6 years (range = 12-83). The mean duration of the surgical procedure was 41 min (range = 20-100). The procedure was successful in 208/211 cases. Three patients (0.5%) required conversion to a minithoracotomy. The mean length of pleural drainage and hospital stay was 2.3 and 3.7 days, respectively. Histological examination showed 98 benign lesions and 113 malignant lesions (61 metastases and 52 primary lung cancers). This study confirms that radio-guided localization of small pulmonary nodules is a feasible, safe, and quick procedure, with a high rate of success. The spread of the sentinel lymph node technique has increased the availability of technology required for RGTS.

Amoxicillin-bearing microparticles: potential in the treatment of Listeria monocytogenes infection in Swiss albino mice

The present study was aimed at evaluating the effectiveness of amoxicillin-bearing HSA (human serum albumin) and PLGA [poly(lactic-co-glycolic acid)] microparticles in combating Listeria monocytogenes infection in Swiss albino mice. Amoxicillin-bearing HSA microspheres were prepared by chemical cross-linking of a drug/albumin mixture with glutaraldehyde, and PLGA microspheres were prepared by the W/O/W (water-in-oil-in-water) emulsion technique. The microspheres were characterized for their size, ζ potential and entrapment efficiency using SEM (scanning electron microscopy) and a Zetasizer. Release kinetics was performed in a phosphate buffer (pH7.4) at 37°C simulating physiological conditions. Bacterial burden in various vital organs and survival data established enhanced efficacy of PLGA and HSA microspheres as compared with free drug. Among the two delivery systems, PLGA microspheres, when compared with HSA microspheres, imparted better efficacy in terms of reduction in bacterial load as well as increase in survival. The results of the present study clearly demonstrate that microparticles successfully target the infected macrophages and the approach could be well exploited for targeting the intracellular pathogens as well.

Comparison of the stability of Y-90-, Lu-177- and Ga-68- labeled human serum albumin microspheres (DOTA-HSAM)

Microparticles derived from denatured human serum albumin (DOTA-derivatized human serum albumin microspheres, or DOTA-HSAM) are attractive carriers of radionuclides for both therapeutic and diagnostic purposes. In this article, we describe a labeling procedure for diagnostic (Ga-68) and therapeutic (Y-90, Lu-177) radionuclides and report on the results of stability studies of these products. DOTA-HSAM was labeled in 0.5 M ammonium acetate buffer, pH 5.0, containing 0.02 mg/ml detergent. After adding the radionuclide, the mixture was shaken for 15 min at 90°C. Labeling yields and in vitro stability were determined by thin-layer chromatography. For determination of the in vivo stability of Ga-68 and Y-90 DOTA-HSAM, the particles were injected intravenously in Wistar rats. Labeling yields up to 95% in the case of Ga-68 and Lu-177 were achieved. Ga-68-labeled DOTA-HSAM showed high in vitro and in vivo stability. The amount of particle-bound radioactivity of Lu-177 DOTA-HSAM declines slowly in a linear manner to approximately 72% after 13 days. For Y-90, the labeling yield decreased with increasing radioactivity level. We presume radiolysis as the reason for these findings. The labeling of DOTA-HSAM with different radionuclides is easy to perform. The radiation-induced cleavage of the labeled chelator together with the rather short half-life of radioactivity fixation in vivo (3.7 days) is, in our opinion, opposed to therapeutic applications of DOTA-HSAM. On the other hand, the high stability of Ga-68 DOTA-HSAM makes them an attractive candidate for the measurement of regional perfusion by PET.

Labelling of albumin microspheres with <SUP align=right>188</SUP>Re: a possible agent for radiotherapy

Regional administration of labelled particles by intra-arterial infusion is an effective method for endoradiotherapy of tumours. The goal of the study was to develop an efficient method for radiolabelling of biodegradable human serum albumin microspheres with the beta emitter 188Re. The influence of different factors, as the reagents concentration, temperature, time, etc., on reaction yield was studied. Under optimised conditions, after 60 min reaction time, at 95°C, the reaction yield was more than 95%. Labelled microspheres were found to be stable in vitro; 43 h after labelling, 87% of 188Re was bound to the microspheres.

Yttrium-86-labelled human serum albumin microspheres: relation of surface structure with in vivo stability

Radiolabelled particles are an attractive tool in the therapy of malignancies of the liver. We consider particles manufactured from denatured human serum albumin (HSA) as useful carriers of therapeutic radionuclides. Covalent attachment of suitable chelators onto the surface of the spheres promises an easy access to radiolabelled HSA microspheres. We synthesized 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) bearing smooth, medium-rough and rough surfaced HSA microspheres (mean diameter: 25 microm). In vitro stability of 86 Y-labelled particles was determined after incubation in human plasma and in a DTPA challenge experiment. In vivo stability of 86 Y DOTA-HSA microspheres was determined after single intravenous application in rats. Subsequently, the particles were completely trapped in the lung microvasculature. Thus, the lung serves in our experiments as target organ. DOTA-HSA microspheres were 86 Y labelled in reproducible high yields (>95%). No differences between smooth and rough surfaced spheres were found for both DOTA coupling and 86 Y labelling. Labelled microspheres showed high in vitro stability in human plasma and in DTPA solution with only 8+/-1% and 2+/-0% loss of radioactivity from the surface, respectively, 48 h postinjection (pi). The three batches (smooth, medium-rough and rough surfaced microspheres) differed considerably in their radioactivity recovery in the lungs of rats 48 h pi. Smooth particles showed the highest in vivo stability of the radiolabel on the surface of the spheres, presumably because of slower proteolytic degradation. We found that for the preparation of HSA-derived microspheres for radiotherapeutic application, smooth surfaced spheres are superior to rough spheres due to their higher in vivo stability of the radionuclide fixation.

Application of nanosized Fe3O4 in anticancer drug carriers with target-orientation and sustained-release properties

The purpose of this study was to prepare human serum albumin (HSA) microspheres with Fe3O4 magnetic nanoparticles for tumor target therapy. Fe3O4 was obtained by liquid-phase coprecipitation; HSA-coated magnetic particles were attained by solidification at high temperature. The result was that nanosized Fe3O4 is a cubic crystal by XRD and the average size is 18.7 nm; the average size of HSA-coated magnetic particles is 341 nm. Fe3O4 magnetic nanoparticles coated with HSA can be used for targeted-drug carriers with target-orientation and sustained-release properties.

The efficacy of peritoneal lavage at elective abdominal operations

Human serum albumin microspheres of 1 micrometer diameter labelled with technetium-99 m were evaluated as a model for bacteria in two animal species. Peritoneal lavage recovered comparable amounts of an inoculum of microspheres and simultaneously instilled Escherichia coli. A prospective study was undertaken of 38 patients undergoing elective abdominal operations. Three lavages, each of 500 ml normal saline, were used. Over 80 per cent of the saline was recovered in 37 of the 38 patients with a median of 93 per cent. Recovery of microspheres was assessed from above the spleen, from Morison's pouch and from the pouch of Douglas. There was no difference in the recovery rates from the three sites of placement but significantly fewer microspheres were recovered via a right subcostal incision (median 59 per cent) compared with an upper midline incision (median 91 per cent).

A kit for labeling of [ 188Re] human serum albumin microspheres for therapeutic use in nuclear medicine

Intra-arterial infusion of labeled particles is an effective method for local endoradiotherapy of tumors. In this study, we present an efficient method of radiolabeling biodegradable human serum albumin (HSA) microspheres with the short-lived beta-emitter 188Re using a simple and reliable kit. Up to now, it was not possible to label particles with more than 85–90% efficiency. Under optimized reaction conditions, we achieved nearly 100% uptake of 188Re. Using the proposed kit, we added tartrate solution and increased the pH from 2 to 4–5 after 1 h reaction time at 95 °C. The 188Re binding to the particles was found to be stable in vitro.

Labeling and biodistribution of different particle materials for radioembolization therapy with 188Re

Radioembolization of tumors after selective catheterization has been proven to be an effective therapy in nuclear medicine. The goal of the study was to evaluate the 188Re labeling and in vitro and in vivo stability of several representative non-degradable polymeric microspheres and biodegradable particles. The biodistribution after i.v. injection in Wistar rats revealed excellent in vivo stability with low uptake in the non-target tissues over 48 h for some polymeric particles and especially for biodegradable human serum albumin microspheres.

Transcatheter embolization using degradable crosslinked hydrogels

Therapeutic embolization is the selective transcatheter blockage of blood vessels or diseased vascular structures. The majority of current embolization materials in clinical use are permanent. There are clinical situations however, in which temporary embolization is desired. Degradable hydroxyethyl acrylate (HEA) microspheres have been synthesized. Canine renal arteries and rabbit central auricular arteries were embolized with HEA microspheres, and compared with degradable human serum albumin (HSA) microspheres, and permanent microspheres. HSA and HEA microspheres both achieved temporary occlusions. HSA and HEA microspheres were recanalizated at 1 and 3 weeks, respectively, while arteries occluded with permanent microspheres did not recanalize. All embolic microspheres led to tissue infarction, with the short-term HSA microspheres providing the least damage, and the permanent microspheres leading to extensive damage. Advantages of temporary embolization were not convincingly demonstrated since temporary occlusions still led to tissue infarction.

Is nuclear medicine really safe?

In nuclear medicine, radiation absorbed dose estimates calculated by standard models at the whole body or organ are very low. At cellular level, however, the heterogeneity of radionuclide distributions of radiation dose patterns may be significant. We present here absorbed doses at cellular level and evaluate their possible impact on the usually assumed risk/benefit relationships in nuclear medicine studies. The absorbed dose values calculated are surprisingly high, and are difficult to interpret. In the present study, we show calculated doses at the cellular level and discuss possible biological consequences, for two radiopharmaceuticals labelled with technetium-99m: human serum albumin microspheres used for pulmonary scintigrapies and HMPAO used to labelled leukocytes.

A pilot study of the role of TC-99 radionuclide in localization of pulmonary nodular lesions for thoracoscopic resection.

Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for diagnosis and treatment of peripheral pulmonary nodules. However, thoracoscopy has limits in the detection of small nodules, below the pleural surface, deep in the lung parenchyma, which cannot be seen as much as palpated. Methods to localize such lesions, including the methylene blue injection or the introduction of a hooked-wire under the radiological vision, have some advantages but a lot of limitations. We are developing a new technique for the detection of pulmonary nodules smaller than 2 cm, deep in the lung parenchyma. The technique consisted of a intra-lesional injection of 0.3 ml of solution of 99m Tc-labelled human serum albumin microspheres (5-10 MBq) under the CT-scan guide, 2 h before surgery. During thoracoscopy a 11 mm diameter-collimated probe connected to a gamma ray detector (Scinti Probe MR 100 - Pol. hi.tech., Aquila - Italy), is introduced by a 11.5 mm trocar and the pleural surface of the suspected area was scanned. A hot-spot indicated the presence of the injected nodule and as a consequence, the area to be resected. from June 1997 to June 1999 we treated 39 patients with small pulmonary nodules. The patients were 27 men and 12 women with a mean age of 60.8 years (range: 13-80). In 19 cases the anamnesis was positive for synchronous or metachronous malignant neoplasm. The mean surgical procedure length was 50 min (range 20-100 min). In all the cases the nodule was resected and the resection margins were pathologically free of tumour. The mean post-operative hospital stay was 3 days (range 2-6 days). Histological examination showed 21 benign lesions and 18 malignant lesions (seven metastases and 11 primary lung cancers). Nine pts with primary lung carcinoma underwent a completion lobectomy by open surgery. Radiolocalization by gamma-probe allows the detection and exeresis of small nodules in a easy and safe way. Future and predictable advances in radio-marked monoclonal antibodies, as well as in the development of endoscopic beta-detector probe, will offer a more effective method for detection of primary and metastatic tumours, targets of thoracoscopic resections.

Gamma probe-guided thoracoscopic surgery of small pulmonary nodules.

Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for the diagnosis and treatment of peripheral pulmonary nodules. We developed a new radioguided surgical technique for the detection during VATS of pulmonary nodules smaller than 2 cm, situated deep in the lung parenchyma and neither visible nor palpable with endoscopic instruments. The procedure is divided into two phases. Two hours before surgery 0.3 ml of a solution composed of 0.2 mL of 99mTc-labeled human serum albumin microspheres (5-10 MBq) and 0.1 mL of non-ionic contrast is injected into the lesion under CT guidance. Then the patient is submitted to VATS. During thoracoscopy a collimated probe of 11 mm diameter connected to a gamma ray detector is introduced via an 11.5 mm trocar and the pleural surface of the suspected area is scanned. A hot spot indicates the presence of the radiolabeled nodule and hence the area to be resected. We treated 39 patients with small pulmonary nodules (mean size, 8.3 mm; range, 4-19 mm). The patients were 27 men and 12 women (mean age, 60.8 years; range, 13-80 years). Nineteen patients had a history of synchronous or metachronous malignancy. In all cases the nodule was detected and resected and the resection margins were pathologically free of tumor. Histological examination showed 21 benign and 18 malignant lesions (7 metastases and 11 primary lung cancers). Nine patients with a frozen section-based histopathological diagnosis of lung cancer without functional contraindications underwent a completion lobectomy by open surgery in the same surgical session. In conclusion, the radiolocalization of small pulmonary nodules by gamma probe during VATS is a safe and easy procedure, with fewer complications and a lower failure rate than other localization techniques.