Radiotracer Localization Research Articles

188 Re-N-DEDC Lipiodol for Treatment of Hepatocellular Carcinoma (HCC)-A Clinical and Prospective Study to Assess In-Vivo Distribution in Patients and Clinical Feasibility of Therapy.

Objective The incidence of inoperable hepatocellular carcinoma (HCC) with/without malignant portal vein thrombosis (PVT) is increasing in India for the last decade; thus, Bhabha Atomic Research Centre (BARC), Mumbai, India, developed diethydithiocarbamate (DEDC), a new transarterial radionuclide therapy (TART) agent. 188 Re-N-DEDC lipiodol is an emerging radiotherapeutic agent for inoperable HCC treatment due to its simple and onsite labeling procedure, cost-effectiveness, and least radiation-induced side effects. This study aimed to evaluate in-vivo biodistribution and clinical feasibility of 188 Re-N-DEDC lipiodol TART in HCC and optimization of labeling procedure to assess post-labeling stability and radiochemical yield of labeled lipiodol with 188 Re-N-DEDC complex. Materials and Methods DEDC kits were obtained as gift from BARC, Mumbai. Therapy was given to 31 HCC patients. Post-therapy planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were performed to see tumor uptake and biodistribution. Clinical feasibility and toxicity were decided by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). Statistical Analysis Descriptive statistics was done for data using SPSS v22. Values was expressed as mean ± standard deviation or median with range. Results Post-therapy planar and SPECT/CT imaging showed radiotracer localization in hepatic lesions. Few patients showed lungs uptake due to hepato-pulmonary shunt (lung shunt < 10%). Maximum clearance was observed through urinary tract with very less elimination through hepatobiliary route due to slow rate of leaching of tracer. No patient showed myelosuppression or any other long-term toxicity over median follow-up of 6 months. Mean overall % radiochemical yield of 188 Re-N-DEDC lipiodol was 86.04 ± 2.35%. The complex 188 Re-N-DEDC was found to be stable at 37°C under sterile condition over a period of 1 hour without any significant change on the % radiochemical purity (90.83 ± 3.24%, 89.78 ± 3.67%, 89.22 ± 3.77% at 0, 0.5, 1 hours, respectively). Conclusion Human biodistribution showed very high retention of radiotracer in hepatic lesions with no long-term toxicity with this therapy. The kit preparation procedure is ideally suited for a busy hospital radio-pharmacy. By this procedure, 188 Re-N-DEDC lipiodol can be prepared in high radiochemical yield within a short time (∼45 minutes). Thus, 188 Re-N-DEDC lipiodol can be considered for TART in advanced and/or intermediate HCC.

P02.01 CT Integrated Bronchoscopy Manual Spraying Pigment Labeling to Localize of Small Pulmonary Nodules

Popularization of High Resolution Computed Tomography (HRCT) has greatly improved the detection rate of pulmonary nodules. Video Assistant Thoracic Surgery (VATS) lobectomy (sublobar lung resection in selected patients) has been the standard surgical treatment for these early stage non-small cell lung cancer. Uniportal VATS, a widely used innovative technique in minimally invasive thoracic surgery, makes less incision and also demands more precise intraoperative palpation/localization which is often challenging for small nodules. Various strategies such as the hookwire method, CT fluoroscopy-guided bronchoscopic dye marking, contrast median injection, radiotracer localization and a virtual assisted lung mapping technology (VAL-MAP). While they provide new options of nodule location for thoracic surgeons, all of these strategies require expensive hardware or software and additional two or three more doctors which are often not affordable for centers with limited resources. The purpose of this study is to develop a practically cheap method of pigment labeling for bronchoscope with no additional need of medical equipment and medical human resources. This is an ethic committee approved clinical trial. Medically operable patients with the HRCT detected small nodules were eligible. This nodule localization method involved a manual drawing the route by the surgeon/bronchoscopist, through a series of bronchial opening sketches and marking the leading bronchus at every bifurcation point based on the HRCT. Two to four appropriate bronchial pathways were selected for each lesion. A metal-tip catheter was inserted into a selected bronchus and advanced to the pleura. The location of the catheter tip was fluoroscopically confirmed, and 1 mL of diluted methylene blue was injected for each marking. All these procedures were completed by one doctor and one nurse. Then low dose CT scan was used to visualize the localization of the multiple markings, which were used as references in the subsequent operation. Success rate and procedure related complication are reported. From April 2019 to July 2020, 18 lesions in 17 patients were enrolled. All surgical procedures were performed using uniportal VATS. The lesions ranged in size from 3 to 23mm, 15 (83%) were nodules of Ground Glass Opacity (GGO). The depth ranged from 0 to 19 mm. A total of 57 lung markings were planned. 54 of them (95%) were completed. Of the 3 failed markings, the target bronchus could not be accessed under the bronchoscopy because of improper angle. Fifty-two (91%) were visible during the operations. The 3 unidentified markings were in the same patient, who had been a coal miner and had a severe carbon deposition on his lung and pleura. There was no adverse event associated with this manual marking procedures. All lesions were successfully resected. In 3 patients failed multiple markings, alternative localization was used successfully. This HRCT guided manual drawing method of lesion localization is safe and effective for small nodule localization for lung cancer surgery. Results of this study appears to be better than conventional percutaneous techniques in clinically evident complications. Because it does not need special equipment, it is more suitable for developing countries with limited equipment and human resources.

Imaging Tumor-Infiltrating Lymphocytes in Brain Tumors with [64Cu]Cu-NOTA-anti-CD8 PET.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Various immunotherapeutic approaches to improve patient survival are being developed, but the molecular mechanisms of immunotherapy resistance are currently unknown. Here, we explored the ability of a humanized radiolabeled CD8-targeted minibody to noninvasively quantify tumor-infiltrating CD8-positive (CD8+) T cells using PET. We generated a peripheral blood mononuclear cell (PBMC) humanized immune system (HIS) mouse model and quantified the absolute number of CD8+ T cells by flow cytometry relative to the [64Cu]Cu-NOTA-anti-CD8 PET signal. To evaluate a patient-derived orthotopic GBM HIS model, we intracranially injected cells into NOG mice, humanized cohorts with multiple HLA-matched PBMC donors, and quantified CD8+ tumor-infiltrating lymphocytes by IHC. To determine whether [64Cu]Cu-NOTA-anti-CD8 images brain parenchymal T-cell infiltrate in GBM tumors, we performed PET and autoradiography and subsequently stained serial sections of brain tumor tissue by IHC for CD8+ T cells. Nontumor-bearing NOG mice injected with human PBMCs showed prominent [64Cu]Cu-NOTA-anti-CD8 uptake in the spleen and minimal radiotracer localization to the normal brain. NOG mice harboring intracranial human GBMs yielded high-resolution PET images of tumor-infiltrating CD8+ T cells. Radiotracer retention correlated with CD8+ T-cell numbers in spleen and tumor tissue. Our study demonstrates the ability of [64Cu]Cu-NOTA-anti-CD8 PET to quantify peripheral and tumor-infiltrating CD8+ T cells in brain tumors. Human CD8+ T cells infiltrate an orthotopic GBM in a donor-dependent manner. Furthermore, [64Cu]Cu-NOTA-anti-CD8 quantitatively images both peripheral and brain parenchymal human CD8+ T cells.

MA06.11 CT-Guided Percutaneous Radiotracer Localization and Resection of Indistinct/Small Pulmonary Lesions

MA06.11 CT-Guided Percutaneous Radiotracer Localization and Resection of Indistinct/Small Pulmonary Lesions

Radioguided lung lesion localization: introducing a fluoroscopy system in a SPECT/CT scan.

The purpose was to report our experience in the use of radiotracer localization and resection of small, indistinct, or nonpalpable pulmonary lesions. We developed an innovative technique implementing a fluoroscopy system on a single-photon emission computed tomography/computed tomography (SPECT/CT) scan that allowed to perform CT-guided injection of radiotracer directly on SPECT/CT. Patients were selected for the radiotracer procedure in presence of difficulties in locating nodules with video-assisted thoracoscopic surgery (VATS). Overall, 0.2 ml of technetium-99m macroaggregated albumin and 0.3 ml of nonionic iodinated contrast were injected under CT guidance. During the VATS procedure, an endoscopic gamma detecting probe was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. Between January 2016 and October 2018, 37 patients underwent CT-guided radiotracer injection. The mean nodule size was 11 mm. CT nodule morphology characteristics were as follows: 15 nodules were ground glass, 12 were solid, and 10 were partly solid. No significant adverse events occurred. In one patient, the surgeons decided for an open thoracotomy after unsuccessfully VATS. Overall, lobectomy was performed in two patients, segmentectomy in one, and wedge resection in 33 patients. No mortality occurred. The pathological diagnosis was 15 (42%) primary lung cancer, eight (22%) metastases, and 13 (36%) benign lesions. Radioguided pulmonary nodule localization is a reliable procedure with a high rate of success, minimal complications, and lower risk of failures, with no associated mortality or significant morbidity. Our SPECT/CT system is the first to benefit from the technological improvement with successfully implementation and application of fluoroscopy to SPECT/CT.

Computed Tomography-Guided Percutaneous Radiotracer Localization and Resection of Indistinct/Small Pulmonary Lesions

Detection of small pulmonary lesions has increased, and often they are difficult to localize and resect. We present our mature experience with preoperative computer tomography-guided radiotracer localization, followed by resection of these lesions. Patients with pulmonary nodule smaller than 1 cm or deep below the visceral pleura underwent computer tomography-guided injection of radiotracer technetium macroaggregates in or close to the lesion. A gamma probe was used to localize the marked area that was resected, and in case of primary lung cancer a lobectomy with nodal dissection was performed. Between November 2007 and December 2017, 262 patients (196 men; median age 63 years) underwent preoperative radiotracer injection with a successful marking in all patients. Complications included 35 asymptomatic pneumothoraxes (13.4%), 36 parenchymal hemorrhage suffusions (13.7%), and 2 mild allergic reactions to contrast medium (0.7%). In all cases, except for 3, the gamma probe revealed the pulmonary lesion. Mean distance from the pleura was 10 mm (range, 0 to 40 mm). Pulmonary resection was performed by thoracoscopy in 212 cases (80.9%), intentional thoracotomy in 42 (16.0%), and converted thoracoscopy in 8 (3.1%). Mean pathologic nodule size was 9.3 mm (range, 2.5 to 39 mm). One hundred sixty-six nodules (63.4%) were nonsolid, 64 (24.4%) were partially solid, and 32 (12.2%) had a solid morphologic characteristic. Histologic examination showed 16 benign (6.1%) and 246 malignant (93.9%) lesions (218 primary lung cancers). Preoperative radiotracer localization of small or indistinct pulmonary lesions is simple and feasible with a high rate of success. It may be an effective and attractive alternative in managing lung lesions.

Radiotracer localization of nonpalpable pulmonary nodules: A single-center experience

ObjectiveMultiple localization techniques to facilitate intraoperative identification of small or nonsolid pulmonary nodules have been developed. Radiotracer localization using technetium-labeled macroaggregated albumin has been our preferred localization method since 2009. We report our experience, including technical pitfalls and modifications, of our initial 77 patients who underwent this technique. MethodsAll patients undergoing preoperative radiotracer localization were identified from a prospective database. Medical records were retrospectively reviewed for patient demographic characteristics, nodule characteristics, procedure details, pathologic data, and outcomes. ResultsSeventy-seven patients underwent localization of 79 pulmonary nodules. Radiotracer localization had an overall success rate of 95%; however, 2 patients required a second localization procedure on the same day. Most failures occurred in nodules that were < 5 mm from the pleural surface, resulting in pleural spillage. Seventy-three patients underwent a diagnostic wedge resection, with 2 of these patients requiring 2 wedge resections. In 2 patients, the nodules were successfully localized; however, they were too deep for wedge resection and required anatomic resection. Two patients did not undergo resection. One patient developed pleural spillage and hemothorax and due to subsequent comorbidities, was never rescheduled. The second patient did not tolerate single-lung ventilation. The majority (86%) of lesions were malignant. Median length of stay was 2 days (range, 1-15 days). There was no 30-day mortality. The only morbidity was a prolonged air leak (>5 days) in 5 patients. ConclusionsRadiotracer localization is a simple and effective technique for intraoperative identification of small pulmonary nodules.

Radio-Guided Localization and Resection of Small or Ill-Defined Pulmonary Lesions

Screening programs have increased the identification of small or indistinct pulmonary lesions that are difficult to localize. We report our experience in their preoperative localization by radiotracer and resection. Patients with pulmonary nodules of subsolid morphology or smaller than 1 cm, deeper 1 cm below the visceral pleura, or both underwent computed tomography (CT)-guided injection of radiotracer technetium 99m macroaggregates in the vicinity of the lesion. During the operation, a handheld gamma probe was used to detect the hot spot where the radioactive tracer was localized, and this area was resected. From November 2007 to May 2013, 112 patients (58 men; median age 62 years) underwent preoperative radiotracer injection with a successful marking in all patients. Adverse events included 33 (29.4%) pneumothoraces (one requiring chest tube placement), 23 (20.5%) parenchymal hemorrhage suffusions, and 1 (0.9%) allergic reaction to contrast medium. In all cases except two, the gamma probe revealed pulmonary lesions. Overall, 123 pulmonary nodules were localized and resected. The mean distance from the pleura was 12 mm (range, 0 to 39 mm). Pulmonary resection was performed by thoracoscopy in 70 (62.5%) cases, thoracotomy in 36 (32.1%), and conversion of thoracoscopy to thoracotomy in 6 (5.4%). The mean nodule size was 9 mm (range, 3 to 24 mm). Histology showed 14 (11.4%) benign lesions and 109 (88.6%) malignant lesions (85 primary lung cancers and 24 metastases). Radiotracer localization of pulmonary lesions is a simple and feasible procedure with a high rate of success. Optimal candidates are patients with suspicious-looking nodules detected by screening or incidental CT resulting frm the high rate of nonsolid morphology and small size.

Carbon-11 labeled cathepsin K inhibitors: syntheses and preliminary in vivo evaluation.

Cathepsin K is a cysteine peptidase primarily located in osteoclasts, cells involved in normal growth and remodeling of bone but that are also responsible for bone loss in osteolytic diseases such as osteoporosis. In vivo imaging of cathepsin K may provide a method to assess changes in osteoclast numbers in such disease states. To that end, two high-affinity and selective cathepsin K inhibitors were radiolabeled with carbon-11. In vivo microPET imaging studies demonstrated uptake and prolonged retention of radioactivity in actively growing or remodeling bone regions (e.g., distal ulnar, carpal, distal and proximal humeral, distal femur, proximal tibia, tail vertebrae). Uptake into bone could be blocked by pre- or co-injection of unlabeled ligand, supporting a specific and saturable binding mechanism for radiotracer localization. These proof-of-concept studies indicate that radiolabeled cathepsin K inhibitors may have potential as in vivo imaging radiotracers for assessing changes of osteoclast numbers in osteolytic diseases.

Utility of bone scintigraphy in diagnosis of post- traumatic osteitis pubis

Minor musculoskeletal injuries usually heal within few weeks with conservative treatment, but in pelvic injuries, symptoms may persist for long duration and patient need medical attention to get relief from disturbing pain symptoms. We present a case of post-trauma osteitis pubis in a 58-year-old female, who reported with lower abdominal and left side hip joint pain since 2 months, after an episode of trivial trauma to her pelvis. Technetium-99m methylene diphosphonate bone scintigraphy was performed, which confirmed the site of injury in symphysis pubis and left hip joint, by increased radiotracer localization at both of these symptomatic sites.

Computed Tomography-Guided Preoperative Radiotracer Localization of Nonpalpable Lung Nodules

We describe preoperative computed tomography (CT)-guided injection of radiotracer technetium (99m) macroaggregates ((99m)Tc-MAA) in challenging small lung nodules, intraoperative localization, and resection. Between November 2007 and February 2010, 44 patients with 47 lung nodules which were detected incidentally or at screening and that were (18)F-fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) positive or increasing in size at subsequent CT scans were candidates for surgical biopsy. Inclusion criteria for preoperative percutaneous CT-guided (low-dose technique) (99m)Tc-MAA localization included having at least one of the following characteristics: nodule size less than 1 cm, subsolid morphology, or distance from the pleura greater than 1 cm. Mean nodule size was 11 mm (range, 5 to 24 mm); 24 nodules were nonsolid, 15 nodules were partially solid, and 8 nodules had a solid morphology. Mean distance from the pleura was 11 mm (range, 0 to 35 mm). Localization complications included 13 minor asymptomatic pneumothoraces, 9 parenchymal hemorrhage suffusions, 1 mild allergic reaction to contrast medium, and 2 patients with chest pain after the procedure. Nine patients had mild extravasation of radiotracer into the pleura. In 2 cases, there was an extravasation of a significant quantity of radiotracer into the pleural cavity. Thoracoscopic biopsy was performed in 30 cases, 2 cases were converted to thoracotomy, and 12 patients underwent intentional thoracotomy. Asymptomatic subjects with suspicious nodules detected by screening or incidental CT are best candidates due to small lesion size and high percentage of nonsolid morphology, making thoracoscopic biopsy potentially difficult. Radiotracer localization is a safe, versatile, simple technique to help perform diagnosis with a minimally invasive approach in nonpalpable lung lesions.

Evaluation of a 99mTc-Labeled Cyclic RGD Tetramer for Noninvasive Imaging Integrin αvβ3-Positive Breast Cancer

Integrin alphavbeta3 plays a critical role in tumor angiogenesis and metastasis. Radiolabeled RGD peptides that are integrin alphavbeta3-specific are very useful for noninvasive imaging of integrin expression in rapidly growing and metastatic tumors. In this study, we determined the binding affinity of E{E[c(RGDfK)]2}2 (tetramer) and its 6-hydrazinonicotinamide conjugate (HYNIC-tetramer) against the binding of 125I-echistatin to the integrin alphavbeta3-positive MDA-MB-435 breast cancer cells. The athymic nude mice bearing MDA-MB-435 xenografts were used to evaluate the potential of ternary ligand complex [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] (TPPTS = trisodium triphenylphosphine-3,3',3' '-trisulfonate) as a new radiotracer for imaging breast cancer integrin alphavbeta3 expression by single photon emission computed tomography (SPECT). It was found that the binding affinity of tetramer (IC50 = 51 +/- 11 nM) was slightly higher than that of its dimeric analogue (IC50 = 78 +/- 27 nM) and is comparable to that of the HYNIC-tetramer conjugate (IC50 = 55 +/- 11 nM) within the experimental error. Biodistribution data showed that [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] had a rapid blood clearance (4.61 +/- 0.81 %ID/g at 5 min postinjection (p.i.) and 0.56 +/- 0.12 %ID/g at 120 min p.i.) and was excreted mainly via the renal route. [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] had high tumor uptake with a long tumor retention (5.60 +/- 0.87 %ID/g and 7.30 +/- 1.32 %ID/g at 5 and 120 min p.i., respectively). The integrin alphavbeta3-specificity was demonstrated by co-injection of excess E[c(RGDfK)]2, which resulted in a significant reduction in tumor uptake of the radiotracer. The metabolic stability of [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] was determined by analyzing urine and feces samples from the tumor-bearing mice at 120 min p.i. In the urine, about 20% of [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] remained intact while only approximately 15% metabolized species was detected in feces. SPECT images displayed significant radiotracer localization in tumor with good contrast as early as 1 h p.i. The high tumor uptake and fast renal excretion make [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] a promising radiotracer for noninvasive imaging of the integrin alphavbeta3-positive tumors by SPECT.

Clinical Experience With Radiotracer-Guided Thoracoscopic Biopsy of Small, Indeterminate Lung Nodules

Although computed tomography lung-screening programs report a 31% to 51% incidence of subcentimeter pulmonary nodules, 85% are too small to biopsy or interrogate with positron emission spectroscopy scans. We developed a technique using transthoracic percutaneous radiotracer injection with thoracoscopic radioprobe localization and excision for small pulmonary nodules. This report describes our series of the first 46 patients evaluated with this technique. Forty-six patients (79% smokers; 52% males; median age, 64 years) were evaluated. Patient selection was based on the surgeon's anticipated difficulty in thoracoscopically locating small nodules because of lesion size or location. Computed tomographic-guided injection of radiotracer solution was made into or adjacent to the nodule the day of surgery. Intraoperative gamma probe localization, followed by thoracoscopic excision of the lesion, was subsequently performed. Median nodule size was 9 mm (range, 3 to 22 mm), and median depth was 5 mm (range, 0 to 50 mm). Forty-four (96%) of the lesions were successfully localized and excised. Median time from injection to surgery was 270 minutes. Failures were the result of inadvertent pleural or chest wall radiotracer placement. Forty-six percent (21 of 46) of the lesions were malignant, of which 71% (15 of 21) were primary lung cancers. Patients with lung cancer underwent lobectomy or segmentectomy. Fourteen of 15 were stage IA, whereas 1 was stage IIIB (6 mm primary with 4 mm intralobar metastasis). Complications were three pneumothoraces at the time of radiotracer injection. Computed tomography-guided radiotracer localization of small pulmonary nodules combined with thoracoscopic excisional biopsy is feasible and safe. This technique successfully localized and excised the nodule in 96% of cases.

Invited commentary

In this article, Daniel and colleagues describe preoperative CT guided radiotracer localization of small pulmonary nodules using 99mTc MAA prior to thoracoscopic wedge resection. The common preoperative marking methods—hookwire placement or methylene blue dye injection—are generally good but not without failures or complications. Hookwire displacement or inability to recognize methylene blue dye on the pleural surface are responsible for considering conversion to open surgery. Radioguided searching allowed detection of all injected lesions. Technetium compounds have long half-lives (6 hours), so it is suitable for preoperative localization and some delay between labeling and operation.Several marking techniques using a radiotracer—specially human serum albumin, tin colloid, phytate, and sulfa colloid—for thoracoscopic resection of small pulmonary nodules have already been reported. One of the most important concerns for localizing of small pulmonary nodules using radiotracer is “the size of particle”. Diffusion of the injected radioisotope, which is dependent on the size of particles, causes difficulty during thoracoscopic wedge resection of small pulmonary nodules. As occurs with some dyes, the isotope will not spread into the lung parenchyma or bronchus if it is big enough to remain at the injection site. Radioactivity is detected as small hot spots on the lung surface in patients. To improve this technique, larger radioactive particles may be useful for preventing diffusion of the injected isotope and decrease the dosage of radioactivity.In this study, the authors use the 99mTc MAA with a particle size of approximately 10–50 μm. This radioisotope is larger than that of human serum albumin (approximately 10 nm), sulfa colloid (approximately 100 nm), phytate (approximately 200–100 nm), and tin colloid (approximately 400–1500 nm), used in previous reports. By using larger radioactive particles, the authors succeeded in decreasing the dosage of radioactivity for injection, 0.1 ml/0.3 mCi of 99mTc MAA. This is the most valuable contribution in this article.Preoperative radiolocalization may be one of the effective localization procedures with less complication and failure, and this technique using larger radioactive particles seems to be more suitable than other radiolocalization methods. This study should contribute to the development of preoperative localization methods for small pulmonary nodules for thoracoscopic resection, and is certainly worthy of further study. In this article, Daniel and colleagues describe preoperative CT guided radiotracer localization of small pulmonary nodules using 99mTc MAA prior to thoracoscopic wedge resection. The common preoperative marking methods—hookwire placement or methylene blue dye injection—are generally good but not without failures or complications. Hookwire displacement or inability to recognize methylene blue dye on the pleural surface are responsible for considering conversion to open surgery. Radioguided searching allowed detection of all injected lesions. Technetium compounds have long half-lives (6 hours), so it is suitable for preoperative localization and some delay between labeling and operation. Several marking techniques using a radiotracer—specially human serum albumin, tin colloid, phytate, and sulfa colloid—for thoracoscopic resection of small pulmonary nodules have already been reported. One of the most important concerns for localizing of small pulmonary nodules using radiotracer is “the size of particle”. Diffusion of the injected radioisotope, which is dependent on the size of particles, causes difficulty during thoracoscopic wedge resection of small pulmonary nodules. As occurs with some dyes, the isotope will not spread into the lung parenchyma or bronchus if it is big enough to remain at the injection site. Radioactivity is detected as small hot spots on the lung surface in patients. To improve this technique, larger radioactive particles may be useful for preventing diffusion of the injected isotope and decrease the dosage of radioactivity. In this study, the authors use the 99mTc MAA with a particle size of approximately 10–50 μm. This radioisotope is larger than that of human serum albumin (approximately 10 nm), sulfa colloid (approximately 100 nm), phytate (approximately 200–100 nm), and tin colloid (approximately 400–1500 nm), used in previous reports. By using larger radioactive particles, the authors succeeded in decreasing the dosage of radioactivity for injection, 0.1 ml/0.3 mCi of 99mTc MAA. This is the most valuable contribution in this article. Preoperative radiolocalization may be one of the effective localization procedures with less complication and failure, and this technique using larger radioactive particles seems to be more suitable than other radiolocalization methods. This study should contribute to the development of preoperative localization methods for small pulmonary nodules for thoracoscopic resection, and is certainly worthy of further study.

A novel technique for localization and excisional biopsy of small or Ill-defined pulmonary lesions

Background The purpose of this study was to develop and evaluate radiotracer-guided localization of small or ill-defined pulmonary nodules for thoracoscopic excisional biopsy. Methods This study consisted of two parts: a laboratory study in rats to determine the most suitable radiotracer, and a pilot study in humans to determine the feasibility of radiotracer lung nodule localization. The right lung of 12 rats was injected with a technetium 99m (Tc 99m) based radiotracer solution: 4 each with macroaggregated albumin (MAA), unfiltered sulfur colloid (SC), and pertechnetate (TcO 4). Serial imaging was performed using a small animal gamma camera for 4 hours following injection. In 13 patients, computed tomographic (CT) guided injection of Tc 99m MAA solution was made into or adjacent to a pulmonary nodule suspicious for primary lung cancer. Gamma probe localization of the nodule was performed during subsequent thoracoscopic surgery. Results In the animal model, MAA provided more precise localization than SC or TcO 4 and was selected for the human study. In the human series, all 13 patients had successful gamma probe localization of their lesion. There were no radiologic or surgical complications. Seven of 13 nodules were malignant, and five of these nodules were stage IA primary lung carcinomas. Conclusions Computed tomographic-guided radiotracer localization of small or ill-defined pulmonary nodules using Tc 99 m MAA before thoracoscopic excisional biopsy is feasible and may make excisional biopsy the preferred management strategy for the management of small pulmonary nodules in patients at high risk for malignancy.

11C-Fallypride: radiosynthesis and preliminary evaluation of a novel dopamine D2/D3 receptor PET radiotracer in non-human primate brain

Fallypride [benzamide, 5-(3-fluoropropyl)-2,3-dimethoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]-, CAS RN 166173-78-0] is a selective dopamine D2/D3 receptor antagonist. Carbon-11 labeled fallypride may serve as a radiotracer for use in biomedical imaging technique positron emission tomography (PET). The precursor, 5-(3-fluoropropyl)-2-hydroxy-3-methoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]benzamide was synthesized from 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid, methyl ester in seven steps with approximately 10% overall chemical yield. Using this precursor 11C-fallypride was produced by radiolabeling with 11C-methyl iodide in 25–40% radiochemical yields with specific activities of 200–1000 Ci/mmol. PET imaging studies in nonhuman primates with 11C-fallypride showed radiotracer localization in dopaminergic brain regions such as caudate, putamen, thalamus and cortex. This regional localization of 11C-fallypride is similar to that observed previously for 18F-fallypride. The results suggest 11C-fallypride is a useful PET radiotracer for imaging dopamine D2/D3 receptors.

A new agent, blue and radioactive, for sentinel node detection.

Although with some disadvantages, combining radiotracer and isosulfan blue facilitates the detection of sentinel lymph nodes. This study was designed to evaluate the use of (99m)Tc-labeled phthalocyanine tetrasulfonate ((99m)Tc-PCTS) as a single agent for simultaneous blue staining and radiotracer localization of the sentinel lymph node. Twelve rabbits were injected into the dermis and subcutaneously in the distal hind limb with 1 mL of blue (99m)Tc-PCTS (.5 mCi). The popliteal and inguinal fossae were explored between 15 minutes and 24 hours after injection for blue and/or radioactive tissue. Popliteal and inguinal fossae and other lymph nodes and organs were harvested for determination of the concentration of radioactivity and for histology. Within minutes of (99m)Tc-PCTS injection, the lymphatic channels were easily identified by the blue color. At 10 minutes, the radioactive count over the popliteal fossa was significantly higher than over other areas. At exploration, a blue and radioactive popliteal node was identified in all animals; inguinal nodes were neither blue nor radioactive. At death, the radioactivity in the popliteal node was 1000 times higher than in other nodes or organs. Although fainter, the blue color in the popliteal node was still visible at 6 weeks. Histological sections of popliteal node identified the dye in the cytoplasmic compartment of the cells. Technetium-99m PCTS is a single agent that identifies sentinel lymph nodes by color and radioactivity and is retained for an extended period of time without migrating to other tissues.

Lymphoscintigraphy of melanoma: lymphatic channel activity guides localization of sentinel lymph nodes, and gamma camera imaging/counting confirms presence of radiotracer in excised nodes.

Lymphoscintigraphy has become a standard preoperative procedure to map the cutaneous lymphatic channel for progression of nodal metastasis of melanoma of the skin. Lymphoscintigraphy was employed to visualize lymphatic channels as a guide to identify sentinel lymph nodes (SLNs). Excised tissue was imaged with a gamma camera to verify the findings of presurgical lymphoscintigraphy. Percent counts of SLN(s) among the total counts of the excised melanoma tumor or scar tissue and SLN(s) were calculated. Eleven patients with cutaneous melanoma received four to ten intradermal injections of Tc-99m sulfur colloid at elual distances around the melanoma site. Images were made immediately after injection: 1 minute per image for 15 min; and then 5 minutes or 1,000,000 counts per image for 30 min. After surgery, the excised melanoma tumor or scar and SLN(s) were imaged/counted with a gamma camera. Percent counts of SLNs among the total counts of the excised melanoma tumor or scar tissue and SLNs were calculated. To validate the specimen count accuracy, an experimental phantom study was done. Linear lymphatic channels were identified between the injected sites and the SLNs in each patient. Gamma camera images demonstrated radioactivity in the SLNs of all patients, verifying the lymphoscintigraphy findings. Uptake in the SLNs of ten of the eleven patients ranged from 0.4 to 7.2% (mean 2.2%) of the total counts in excised tissue. We noted that a node with lower uptake should not be ignored because a lower percent of SLN activity does not necessarily rule out existing metastasis. In two of eleven patients, histopathologic showed metastases. One patient's melanoma on the middle back had lymphatic channel activity directed to both axillae. The results of the phantom study validated accuracy of our specimen counts. Because linear lymphatic channels existed between lymph nodes and the injected sites in all eleven patients, these lymphatic channels could be used as a guide for localizing SLNs. The SLNs indicated by presurgical lymphoscintigraphy were verified by postoperative gamma camera imaging, and radiotracer localization in the SLNs averaged 2.2%.

Artifact of cold lesions on skull SPECT of a patient with Paget's disease secondary to pixel overflow.

Various SPECT imaging artifacts have been described. One of them is pixel overflow caused by excessive radiotracer deposition in bone, resulting in areas of very low or absent activity on SPECT. Paget's disease of bone is characterized by intense and extensive radiotracer localization on bone imaging. A patient with Paget's disease is described whose planar bone scintigraphy and radiography showed osteoblastic and sclerotic areas of the skull, whereas SPECT showed photopenic and photon-deficient areas interposed with diffuse uptake in the skull. This indicates that bone SPECT might give artifacts of cold lesions secondary to pixel overflow as a result of excessive radiotracer deposition.

Extensive Extraosseous Localization of Bone Imaging Agent in a Patient with Renal Failure and Rhabdomyolysis Accompanied by Combined Hypercalcemia and Hyperphosphatemia

Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel. In studies done two months later (in the third study), the radioactivity in the skeletal muscles was no longer seen. Studies obtained nine months (in the fourth study) after the first imaging showed less radiotracer localization in the LV, lungs, and kidneys as compared to that seen in the initial study. Myocardial necrosis and microcalcification were proved by LV biopsy. The exact mechanism of extraosseous bone-imaging agent localization is unknown. However, this phenomenon may be related to renal failure, rhabdomyolysis, hypercalcemia, hyperphosphatemia, or elevated parathyroid hormone. The Tc-99m PYP imaging study is useful and sensitive in the detection of extraosseous tissue calcification and monitoring of the disease process.