Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis.

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. BACKGROUND: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. METHODS: A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method. RESULTS: Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. CONCLUSIONS: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.

A feasibility study of sentinel lymph node mapping by cervical injection of a tracer in Japanese women with early stage endometrial cancer.

OBJECTIVE: The aim of this study was to investigate the feasibility of sentinel lymph node mapping characterized by a cervical tracer injection in endometrial cancer. MATERIALS AND METHODS: This retrospective study was carried out using data for 57 patients with endometrial carcinoma who had undergone intraoperative sentinel lymph node mapping and subsequent surgical staging. Technetium colloid and/or indocyanine green was injected into the uterine cervix and a gamma-detecting probe and/or photodynamic eye camera system was used intraoperatively to locate hot spots. RESULTS: Of the 57 patients, 52 (91.2%) had FIGO Stage I disease. Successful unilateral or bilateral mapping occurred in 54 patients (94.7%) and 46 (80.7%), respectively. The median number of sentinel lymph nodes detected was two (range, 0-5). Following sentinel lymph node mapping, 41 patients (71.9%) underwent pelvic lymphadenectomy alone and 16 (28.1%) full lymphadenectomy. The median number of lymph nodes resected was 17 (range, 8-110). Sentinel lymph nodes were involved in four patients (7.0%), two with macrometastases and two with low-volume metastases. The sensitivity and negative predictive value for detecting lymph node metastasis were both 100%. CONCLUSION: Sentinel lymph node mapping with the use of cervical tracer injection is highly feasible in Japanese women with early stage endometrial cancer.

Biochemical, radiological, and genetic characterization of congenital hypothyroidism in Abu Dhabi, United Arab Emirates.

BACKGROUND: Congenital hypothyroidism (CH) is caused by thyroid gland (TG) dysgenesis or inadequate thyroid hormone biosynthesis in a structurally normal gland. Different etiologies are known to be associated with various clinical, biochemical and imaging markers and a subset of cases have an underlying genetic basis. Despite the presence of neonatal screening programs in the UAE, there is a lack of data on the disease etiology in the area. We aim to study the etiology of CH in our center and examine its relationship with the clinical, biochemical, genetic and radiological features. METHODS: Patients with CH who were followed in our center between 2011 and 2014 are enrolled in the study. Data collected included gender, gestational age, history of CH in a first-degree relative, initial thyroid stimulating hormone (TSH) and thyroxine (T4) levels, imaging findings, associated disease/malformation and treatment details. Selected patients with associated systemic disease or familial CH underwent genetic testing. RESULTS: Sixty-five patients were enrolled. Ten patients underwent genetic study: seven patients with associated congenital disease/malformation, one with a sibling and two with cousins with CH. Forty-nine subjects had technetium99 and/or ultrasound scans. Dyshormonogenesis was diagnosed in two-thirds of the patients. Three patients of 10 tested had likely causative genetic mutations; two homozygous thyroid peroxidase (TPO) and one heterozygous thyroid stimulating hormone receptor (TSHR) missense mutations. CONCLUSIONS: Dyshormonogenesis is the commonest etiology in CH in the studied group. It is expected that genetic mutations are more prevalent in our region due to the nature of the CH etiology and the rate of high consanguinity rate.

Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).

Comparative in vitro stability and scintigraphic imaging for trafficking and tumor targeting of a directly and a novel 99mTc(I)(CO)3 labeled liposome.

Liposomes radiolabelling with diagnostic radionuclides is an excellent tool for studying pharmacokinetics with the view of developing liposome-based drug delivery agents. The aim of the present study is to evaluate the in vitro and in vivo behavior of a (99m)Tc-labeled liposome by applying either a direct labeling strategy via a carboxyl group, LP-COOH, or a surface chelating method via pyridyl ethyl cysteine compound (with the intermediate [99mTc(I)(CO)3(H2O)(3)](+)), LP-PEC. 99mTc-LP-COOH was obtained in high radiolabelling yield and radiochemical purity, while 99mTc(I)(CO)3-LP-PEC was initially purified before being in vitro and in vivo evaluated. 99mTc-LP-COOH was less stable in the presence of competitive for 99mTc ligands than 99mTc(I)(CO)3-LP-PEC. According to DLS measurements, the presence of serum as well as the applied radiolabelling conditions did not affect the liposomes' size. The different radiolabelling methods seemed to exert an influence on the biodistribution pattern of the liposomes with the 99mTc(I)(CO)3-LP-PEC showing slow blood clearance, which was also confirmed by in vivo scintigraphic imaging. Nevertheless, passive tumor targeting was attained at a similar extent no matter which radiolabelling technique was followed.

Reproducibility of lymphoscintigraphy before and after excisional biopsy of primary breast lesions: a study using superficial peri-areolar injection of the radiotracer.

OBJECTIVE: A major controversial issue in the sentinel node biopsy of the breast is the applicability of sentinel node mapping in patients with the history of previous excisional biopsy of the breast lesions. In the current study, we evaluated the reproducibility of lymphoscintigraphy before and after excisional biopsy of the primary breast lesions using superficial peri-areolar injection of the radiotracer. MATERIAL AND METHODS: Eighteen patients scheduled for excisional biopsy of breast lesions were included into the study. The patients received intra-dermal injection of the radiotracer in the peri-areolar area of the index quadrant 1 to 2h before surgery. Imaging was performed the day after surgery. Immediately after completion of the first imaging, the patients received another injection of the radiotracer with the same technique, dose, and location. Other sets of lymphoscintigraphy imaging were taken immediately and 4h post second injection. The two sets of lymphoscintigraphy images were compared. RESULTS: In 2 patients, sentinel node could not be identified in either set of images. In the remaining 16 patients, one sentinel node was detected in both lymphoscintigraphy image sets. The sentinel nodes of the second image sets were all in the same location of the first sets with at least 5 times higher count. CONCLUSIONS: Excisional biopsy of the primary breast lesions does not seem to change the superficial lymphatic drainage pattern from the areola of the breast and sentinel node mapping can be performed after this procedure using superficial periareolar technique.

Molecular imaging: challenges of bringing imaging of intracellular targets into common clinical use.

Molecular imaging (MI) takes advantage of several new techniques to detect biomarkers or biochemical and cellular processes, with the goal of obtaining high sensitivity, specificity and signal-to-noise ratio imaging of disease. The imaging modalities bearing the most promise for MI are positron emission tomography (PET), single photon emission computer tomography (SPECT) and different optical imaging techniques with high sensitivity. Also magnetic resonance imaging (MRI) with contrast agents like ultra-small superparamagnetic iron oxide particles (USPIO), magnetic resonance spectroscopy and ultrasound imaging with contrast agents may be useful approaches. MI techniques have been used in the clinic for many years, i.e. PET imaging using (18) F-labeled fluorodeoxyglucose. Animal studies have during the last years revealed great potential for MI also with several other agents. The focus of the present article is the challenges of clinical imaging of intracellular targets following intravenous injection of the agents. Thus, the great challenge of getting enough contrast agent into the cytosol and at the same time obtaining a low signal from tissue just outside the diseased area is discussed.

Factors influencing the time of sentinel node visualization in breast cancer patients using intradermal injection of the radiotracer.

BACKGROUND: The objective of our study was to determine the important factors that have influence on the time of sentinel node visualization using intradermal injection of (99m)Tc-antimony sulfide colloid. METHODS: Two hundred fifty consecutive patients with the diagnosis of early-stage breast cancer were evaluated. Anterior and lateral views were acquired in various intervals after intradermal injection of the tracer until 180 minutes or visualization of the sentinel node. The effect of several variables on the time of sentinel node visualization was evaluated by univariate and multivariate analyses. RESULTS: The time of sentinel node visualization was significantly correlated with age, body mass index (BMI), and interval between biopsy and sentinel node mapping. Standardized beta values for these variables were .1, .3, -.55 respectively. CONCLUSIONS: Older age and higher BMI can result in slow sentinel node visualization. Longer interval between biopsy and sentinel node mapping can be associated with rapid sentinel node detection.

The efficacy of Tc-99m sestamibi for sentinel node mapping in breast carcinomas: comparison with Tc-99m antimony sulphide colloid.

BACKGROUND: To study the value of periareolar intra-dermal injection of Tc-99m sestamibi (MIBI) for sentinel node mapping in breast carcinoma. MATERIAL AND METHODS: Fifty patients with early-stage breast cancer were included in our study. 17.5 MBq Tc-99m-MIBI was injected intradermally to 25 patients and the remainders were injected with the same dose of Tc-99m-antimony sulphide colloid. Anterior and lateral static images were taken at 2 minutes. If sentinel lymph node was not detected, delayed imaging by up to 180 minutes was carried out. The patients were operated on 2-4 hours post-injection. Sentinel lymph node biopsy was performed by the aid of gamma probe and blue dye during surgery. RESULTS: In the Tc-99m-MIBI group, 23 patients had lymph nodes on scintigraphy images, and sentinel nodes were detected during surgery in all 23 patients. In the Tc-99m-antimony sulphide colloid group, 24 patients had lymph nodes on scintigraphy images, and sentinel nodes were identified during surgery in 24 patients. CONCLUSIONS: We concluded that 99mTc-MIBI is a suitable radiopharmaceutical for sentinel node detection.

Sentinel lymph node identification with radiopharmaceuticals in patients with breast cancer: a comparison of 99mTc-tin colloid and 99mTc-phytate efficiency.

Sentinel lymph node biopsy with lymphoscintigraphy has become the standard method for the detection of axillary lymph node metastasis in breast cancer patients. However, there is no standardized radiopharmaceutical. For the detection of axillary lymph node metastasis by lymphoscintigraphy and sentinel node biopsy in patients with breast cancer, we compared the results between subareolar injection of (99m)Tc-tin colloid and injection of (99m)Tc-phytate. This study included 516 breast cancer patients who underwent surgery between 2001 and 2010. Among the 516 patients, (99m)Tc-tin colloid (37-185 MBq) was administered to 412 patients by subareolar injection, and (99m)Tc-phytate (37-185 MBq) was injected in 104 patients. Lymphoscintigraphy was performed with the patients in the supine position, and sentinel node identification was performed by hand-held gamma probe during surgery. Among 412 patients with (99m)Tc-tin colloid, the sentinel node was identified by lymphoscintigraphy in 364 cases (88.3%) and by a gamma probe in 369 cases (89.6%). Among 104 patients with (99m)Tc-phytate, 101 cases (97.1%) were identified by lymphoscintigraphy and 101 cases (97.1%) were identified by a gamma probe. The identification rates by lymphoscintigraphy and gamma probe were superior with (99m)Tc-phytate, as compared with (99m)Tc-tin colloid, with a statistically significant difference (P < 0.05 for both methods). (99m)Tc-phytate is a better choice than (99m)Tc-tin colloid for identification of the sentinel node in breast cancer patients.

Comparison of early and delayed lymphoscintigraphy images of early breast cancer patients undergoing sentinel node mapping.

OBJECTIVE: We compared early and delayed lymphoscintigraphy images using intradermal injection of (99m)Tc-antimony sulfide colloid, which has small particles. METHODS: Eighty patients with early-stage breast cancer were included into the study. Intradermal injection of (99m)Tc-antimony sulfide colloid was used for sentinel node mapping. After radiotracer injection, 30 min and 20 h later, lymphoscitigraphy images were obtained in lateral and anterior views. After the completion of each image sets, the location of the visible nodes in the axilla was marked on the skin. Two nuclear medicine specialists reviewed the images independently and the number and location of detected nodes were recorded. RESULTS: At least one hotspot was detected in the axillary region in 78 (97.5%) and 79 (98.75%) patients on the early and delayed images, respectively. No extra-axillary drainage was noted in the patients. The number and location of detected hot spots were the same in 77 patients on both image sets. In one patient the early image did not show any axillary hot spot despite its visualization on the delayed image set and in one patient no hot spot was noted on either images. In one patient an additional axillary hot spot was noted on the delayed image, which was not apparent on the early image. CONCLUSION: Our study showed that a delay of up to 20 h in sentinel lymph node biopsy using intradermal injection of (99m)Tc-antimony sulfide colloid does not result in washout of the tracer from the true sentinel node or migration of the radiotracer into second-echelon nodes.

Factors affecting sentinel lymph node detection failure in breast cancer patients using intradermal injection of the tracer.

OBJECTIVE: The standard method for axillary lymph node staging in early breast cancer is sentinel lymph node biopsy. In some patients the sentinel lymph node can not be localized during surgery and these patients have to undergo standard axillary lymph node dissection. In this study we have evaluated the predictors of sentinel lymph node localization failure using (99m)Tc-antimony sulfide colloid and intradermal injection combined with blue dye technique. MATERIAL AND METHODS: 202 consecutive patients with early stage breast cancer (clinically stage I or II) were retrospectively evaluated. Patients whose sentinel lymph node was localized during surgery were compared to those with localization failure considering several variables. RESULTS: Sentinel lymph node was successfully located on the pre-operative lymphoscintigraphy images in 180 patients (89%). Both univariate and multivariate analyses showed that only sentinel lymph node non-visualization by pre-operative lymphoscintigraphy, experience of the surgeon, and axillary lymph node involvement are associated with sentinel node localization failure during surgery. CONCLUSIONS: This study shows the importance of pre-operative lymphoscintigraphy in order to identify the group of patients with possible localization failure during surgery and warning the surgeon beforehand. We also recommend that all surgeons pass the learning curve of sentinel lymph node biopsy before routinely performing this procedure.

Comparison of subareolar injection lymphoscintigraphy with the 1-day and the 2-day protocols for the detection of sentinel lymph nodes in patients with breast cancer.

OBJECTIVE: Lymphoscintigraphy and sentinel node biopsy are used for the detection of axillary lymph node metastasis in breast cancer patients. However, currently there is no standardized technique. For the detection of axillary lymph node metastasis by lymphoscintigraphy and sentinel node biopsy, in patients with breast cancer, we compared the results of subareolar injections administered on the day of surgery (1-day protocol) with injections administered on the day before surgery (2-day protocol). MATERIALS AND METHODS: This study included 412 breast cancer patients who underwent surgery between 2001 and 2004. For the 1-day protocol (1 h before surgery) 0.8 ml of Tc-99m Tin-Colloid (37 MBq) was injected in 203 in the subareolar region on the morning of the surgery. For the 2-day protocol (16 h before surgery) 0.8 ml of Tc-99m Tin-Colloid (185 MBq) was injected in 209 patients on the afternoon before surgery. Lymphoscintigraphy was performed in the supine position and sentinel node identification was performed by hand-held gamma probe during surgery. RESULTS: Among 203 patients with the 1-day protocol, 185 cases (91.1%) were identified by sentinel node lymphoscintigraphy, and 182 cases (89.7%) were identified by gamma probe. Among the 209 patients, in the 2-day protocol, 189 cases (90.4%) had the sentinel node identified by lymphoscintigraphy, and 182 cases (87.1%) by the gamma probe. There was no significant difference in the identification rate of the sentinel node between the 1-day and 2-day protocols by lymphoscintigraphy and the gamma probe (p > 0.05, p > 0.05). CONCLUSIONS: The results of the identification of the sentinel node by subareolar injection according to 1-day or 2-day protocol, in breast cancer patients, showed no significant differences. Because the 2-day protocol allows for an adequate amount of time to perform the lymphoscintigraphy, it is a more useful protocol for the identification of sentinel nodes in patients with breast cancer.

Colonoscopic preoperative localization using submucosal injection of radiolabelled colloid.

Malignant colonic polyps can be removed endoscopically but surgical resection is sometimes required. However, the polypectomy site can be difficult to locate. Current methods use various tattooing agents, with varying degrees of success. A new technique using preoperative injection of technetium-99m-labelled antimony colloid, with intraoperative localization using a handheld gamma probe, is described. Although unsuccessful in terms of localizing a previously partially resected polyp, the technique itself proved safe and simple, and has some advantages over other endoscopic approaches.

Successful internal mammary visualization with periareolar injections of Tc-99m antimony sulfur colloid in sentinel node breast lymphoscintigraphy.

PURPOSE: The subareolar and periareolar injection techniques result in higher detection rates and do not require tumor localization in impalpable lesions when compared with the peritumoral technique. One of the main criticisms, however, is the widely reported inability to detect internal mammary nodes. This contrasts with our clinical experience using Tc-99m antimony sulfur colloid, in which internal mammary nodes are commonly seen. METHODS: A retrospective analysis of 241 patients over 38 months was performed to investigate the ability of our periareolar injection technique to detect internal mammary lymph node drainage in breast cancer sentinel node lymphoscintigraphy. Four injections of 5 to 10 MBq (0.14-0.27 mCi) Tc-99m antimony sulfur colloid were administered on the day of surgery followed by massage and imaging. The radioisotope was suspended in 0.1 mL with a 0.5-mL air lock. Each injection was performed over 2 seconds with a 25-gauge needle at a depth of 1.1 to 1.3 cm. Patients whose records could not be retrieved or who underwent an injection technique apart from periareolar or peritumoral were removed from the analysis. RESULTS: One hundred thirty-three patients underwent the periareolar technique, 72 patients underwent the peritumoral technique, and 36 patients were excluded from the analysis. Internal mammary drainage was seen in 24 of 133 (18.0%) patients, of which 12 (9%) were seen only in the internal mammary chain. This is much higher than previous studies quoting 0.0% to 4.3% and is similar to previously reported rates using the peritumoral technique. CONCLUSIONS: Our periareolar injection technique using Tc-99m antimony sulfur colloid is able to detect internal mammary lymph nodes in at least 18.0% of patients.

Novel procedures for preparing 99mTc(III) complexes with tetradentate/monodentate coordination of varying lipophilicity and adaptation to 188Re analogues.

Improved methods are presented for the preparation of 99mTc and 188Re mixed-ligand complexes with tetradentate and monodentate ligands of the general formula [MIII(Lm)(Ln)] (M = Tc, Re; Lm = NS3 or NS3COOH; Ln = isocyanide or phosphine). To avoid the undesired formation of reduced-hydrolyzed species of both metals, the preparation of complexes is performed in a two-step procedure. At first the Tc(III)- or Re(III)-EDTA complex is formed which reacts in a second step with the tripodal ligand 2,2',2' '-nitrilotris(ethanethiol) (NS3) or its carboxyl derivative NS3COOH (a) and the monodentate phosphine ligands (triphenylphosphine L1, dimethylphenylphosphine L2) or isocyanides (tert-butyl isonitrile L3, methoxyisobutyl isonitrile L4, 4-isocyanomethylbenzoic acid-L-arginine L5, 4-isocyanomethylbenzoic acid-L-arginyl-L-arginine L6, 4-isocyanomethylbenzoic acid-neurotensin(8-13) L7) to the so-called '4+1' complex. Copper(I) isocyanide complexes are used for preparing the '4+1' complexes. That facilitates storage stability and allows kit formulations, and, moreover, enables the formation of 188Re complexes in acidic solution. Only micromolar amounts of the monodentate ligand are needed, and that results in high specific activity labeling of interesting molecules. The lipophilicity of complexes can be controlled by introducing a carboxyl group into the tetradentate ligand and/or derivatization of the monodentate ligands. Furthermore, the carboxyl group enables the conjugation of biomolecules. As an example, the neurotensin derivative CN-NT(8-13) was prepared and labeled with 99mTc according to the '4+1' approach, and its behavior in vivo was studied.

CT-guided lymphoscintigraphy in patients with squamous cell carcinoma of the head and neck: a feasibility study.

Accurate knowledge of lymphatic drainage facilitates planning of surgery for patients with squamous cell carcinoma of the head and neck. The aim of this study was to evaluate the feasibility of a new injection technique for lymph node detection in patients with squamous cell carcinoma of the hypopharynx and larynx, in whom simple peritumoural injection is hampered by the tumour localisation. Computed tomography (CT)-guided lymphoscintigraphy was performed in a total of 13 patients with squamous cell carcinoma of the hypopharynx and larynx who could not be injected by simple visual inspection. In a first step, contrast medium-enhanced axial 5-mm-thick CT slices of the neck were obtained. After tumour localisation on these CT images, 1-2 ml contrast medium and, in the event of appropriate distribution, subsequently 50 MBq technetium-99m colloid were injected at one to three peritumoural sites under CT guidance. Peritumoural tracer distribution was controlled by thin-slice CT. Subsequently, planar scintigrams from anterior, right and left lateral views were obtained. In all patients, peritumoural colloid application was feasible, as shown on control CT scans. Post injection, neither severe nor minor complications were noted. The patients complained of only low pain sensations with an average score of 1.8 on a pain scale from 0 to 10. Lymphatic drainage was identified in nine of the 13 patients, with a total of 14 detected lymph nodes. In six patients, ipsilateral sentinel lymph nodes were visualised; bilateral sentinel lymph nodes were identified in one patient and contralateral lymphatic drainage was observed in two patients. CT-guided lymphoscintigraphy is a feasible and minimally invasive diagnostic tool for sentinel lymph node detection in patients with squamous cell carcinoma of the hypopharynx and the larynx. In contrast to endoscopic colloid injection under general anaesthesia, this technique seems to be a well-tolerated method for lymphatic mapping prior to surgical procedures.

Intraoperative location of small gastrointestinal cancers with a handheld gamma probe.

The location of a small lesion must be precisely identified during laparoscopic surgery. A gamma probe that is usually used for navigating sentinel lymph nodes was evaluated for its usefulness in locating small gastrointestinal lesions (14 gastric and 10 colonic). A total of 2 mCi of a Tc(99m)-labeled rhenium colloid was injected endoscopically around a tumor 16 h prior to surgery. During operation, the abdominal cavity was scanned using a handheld gamma probe (Navigator GPS, Tyco HealthCare, Norwalk, CT, USA). In all cases, the injection site was identified as the highest spot in the abdominal cavity, with 2585 counts per second on average (range, 910-8800 counts per second). The highest count in a lymph node was 637 per second on average. The gamma probe is a useful tool for identifying small gastrointestinal lesions during open and laparoscopic operations.