Utility of 'dual phase' cone beam computed tomography during radioembolisation in patients with hepatocellular carcinoma: what is really changing in flow dynamics before and after 90Y delivery?

PURPOSE: The aims of the study were: 1) to compare two phases of dual-phase cone beam computed tomography (DP-CBCT) achieved before and after Yttrium-90 (90Y) administration and to evaluate additional benefits during radioembolisation (RE) procedures; and 2) to compare DP-CBCT with pre-procedure contrast enhanced cross-sectional images in terms of tumour detection. MATERIAL AND METHODS: Twenty-three hepatocellular carcinoma patients undergoing RE treatment were scanned with DP-CBCT consisting of early arterial (EA) and late arterial (LA) phases before and after 90Y administration. The CT-like datasets were compared according to embolisation effect, enhancement patterns, lesion detectability, image quality, and artifacts by two interventional radiologists blinded to each other. The compatibility of the two radiologists was evaluated with kappa statistical analysis, and the difference between EA and LA phases was evaluated with marginal homogeneity test. Also, DP-CBCT images were compared with preprocedural cross-sectional images (CT/MRI). RESULTS: For 23 patients 92 data were acquired. Thirteen patients showed a decrease on post-embolisation images both visually and on Hounsfield unit (HU) measurements. No statistical difference was found for tumour detection between EA and LA phases (p = 1.0). Tumour enhancement was visually superior at LA phases whereas EA phases were better for arterial mapping for selective catheterisation. DP-CBCT images were not inferior to preprocedural cross-sectional imaging findings. CONCLUSIONS: DP-CBCT is a promising tool for predicting tumour response to therapy and is not inferior to preprocedural cross-sectional imaging in terms of tumour detection. It allows better assessment during RE procedures because early phases provide good mapping for superselective catheterisation whereas late phases are better for visualisation of tumour enhancement.

A Case of Pseudoaneurysm of the Internal Carotid Artery Following Endoscopic Endonasal Pituitary Surgery: Endovascular Treatment with Flow-Diverting Stent Implantation.

Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surgery occurring in 0.4-1.1% of cases. Pseudoaneurysms can subsequently result in other complications, such as subarachnoid hemorrhage, epistaxis, and caroticocavernous fistula with resultant death or permanent neurologic deficit. In this case, we illustrate endovascular treatment with a flow-diverting stent for an ICA pseudoaneurysm after endoscopic endonasal surgery for a pituitary adenoma in a 56-year-old male. Surgery was complicated by excessive intraoperative bleeding and emergent CT angiography confirmed an iatrogenic pseudoaneurysm on the anteromedial surface of the ICA. The pseudoaneurysm was treated endovascularly with flow-diverting stent implantation only. Follow-up CT angiography after three months demonstrated occlusion of the pseudoaneurysm.

Evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin.

OBJECTIVE: The aim of this study was to determine whether the use of platelet rich fibrin (PRF) improved the healing of extraction sockets. STUDY DESIGN: A total of 20 patients with bilateral soft tissue impacted mandibular third molars were included in this study. The left and right third molars were extracted during the same session. Subsequently, the PRF membrane was randomly administered to one of the extraction sockets, whereas the contralateral sockets were left without treatment. On postoperative 30. and 90. days, panoramic images and bone scintigrams were taken to evaluate the bone healing between PRF-treated and non-PRF-treated sockets. Also, periodontal evaluation was performed in the same control sessions. Dependent group t test for paired samples was used for statistical analysis. RESULTS: The average increase in technetium-99m methylene diphosphonate uptake as an indication of enhanced bone healing did not differ significantly between PRF-treated and non-PRF-treated sockets 30 and 90 days postoperatively. Radio-opacity that can show the bone healing on panoramic images were measured by Image J programme and they did not differ significantly. Also periodontal values did not differ significantly. CONCLUSIONS: PRF might not lead to enhanced bone healing in impacted mandibular third molar extraction sockets 30 and 90 days after surgery. It is thought that PRF has the potential characteristics of an autologous fibrin matrix and can accelerate the healing. To better understand the effects of PRF on healing, further research is warranted with larger sample sizes.

Recurrent meningitis and frontal encephalocele as delayed complications of craniofacial trauma.

Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus encephalocele as a delayed complication of frontal sinus fracture is seen more rarely. We present a case of frontal encephalocele and recurrent meningitis as delayed complications of craniofacial trauma. Diagnosis, management, and treatment approaches of these complications are discussed.

Squamous cell carcinoma originating from the nasal septal perforation: a rare nasal tumor.

Primary squamous cell carcinoma of the nasal septum is an extremely rare malignancy. In this article, we report a case of 52-year-old female with a complaint of nasal obstruction along with occasional nasal bleeding for one year. Endoscopy showed a 2.5x2 cm perforation originating from the anterior nasal septum. Incisional biopsy result was reported as squamous cell carcinoma. The tumor was removed by functional endoscopic surgery. Histopathological examination revealed squamous cell carcinoma with safe surgery borders. No recurrence and complications were noticed after one year of follow-up. The functional impact of the treatment with high mortality rates highlights the importance of early diagnosis. We recommend the differential diagnosis of septal perforation and early wide surgical excision for such cases.

Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT.

Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG(2000)-PE:Chol:DTPA-PE), (PL 90G:PEG(2000)-PE:Chol:DTPA-PE), (DPPC:PEG(2000)-PE:Chol:PAPs), (PL 90G:PEG(2000)-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3-8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging.

[Anatomical and functional results of open cavity tympanomastoidectomy]. / Açik kavite timpanomastoidektominin anatomik ve fonksiyonel sonuçlari

OBJECTIVES: In this study, we aimed to evaluate the anatomical and functional results of open cavity tympanomastoidectomy due to chronic otitis media with cholesteatoma. PATIENTS AND METHODS: Between January 2003 and October 2009, 166 patients who underwent open cavity tympanomastoidectomy due to chronic otitis media with cholesteatoma in our clinic were retrospectively analyzed. Seventy-two ears of 69 patients (40 males, 29 females; mean age 36.7±17.7 years; range 9 to 64 years) who visited on a regular basis due to acquired middle ear cholesteatoma were included. Cholesteatoma was classified as attic, sinus and tensa retraction cholesteatoma, according to its localization. Audiological findings were compared based on the localization of cholesteatoma and intraoperative ossicular status. RESULTS: The mean follow-up was 36.3±27.0 months (range 6 to 88 months). There were six (8.4%) greft failures, four (5.6%) graft retractions, and one (1.4%) recurrent cholesteatomas in the ears of the patients. There were also five (7%) pearly residual cholesteatomas. At the last visit following surgery, 97.2% of cavities were dry and self-cleaning. The mean preoperative pure tone air threshold was 53.5±22 dB, while it reduced to 52.2±23.3 dB at the last visit in 48 ears operated open cavity tympanomastoidectomy type 1, 2, 3, and 4 in combination with hearing reconstruction (p=0.454). There was a statistically significant reduction in the mean air-bone gap of the attic cholesteatomas, decreasing from 27.2±14.6 dB to 21.6±12.2 dB (p=0.007). Air-bone gap values were lower than 20 dB in 23 (47.9%) of the cases and the gain was more than 10 dB in 17 (35.5%). No statistically significant correlation was found between the localization of cholesteatoma and intraoperative ossicular status (p>0.05). CONCLUSION: Open cavity tympanomastoidectomy, which allows total removal of the pathology, is an applicable surgical approach with satisfactory outcomes for hearing reconstruction.

2009 EANM parathyroid guidelines.

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Analysis of dendritic cells in sentinel lymph nodes of patients with endometrial and patients with cervical cancers.

OBJECTIVE: The aim of this study was to identify the immune response in sentinel lymph nodes (SLNs) of patients with endometrial and patients with cervical cancers by analyzing the number of S-100-, CD1a-, CD83-positive (+) dendritic cells that are the major antigen-presenting cells. METHODS: A total of 56 patients with early-stage cancer (n = 32, with cervical; n = 24, with endometrial cancer) underwent SLN biopsy. Sentinel lymph nodes and non-SLNs were stained with antibodies against S-100, CD1a, and CD83 as markers for dendritic cells to find out whether SLNs were immunomodulated compared with non-SLNs. RESULTS: The mean values of S-100(+) and CD1a(+) dendritic cells in both the tumor-free and the metastatic SLNs were significantly higher than those of both the tumor-free and the metastatic non-SLNs. When metastatic SLNs were compared with nonmetastatic SLNs, CD83(+) dendritic cells were found significantly more abundant in nonmetastatic SLNs. CONCLUSIONS: Significantly higher numbers of S-100(+) and CD1a(+) dendritic cells in the SLNs compared with those in the non-SLNs may indicate that SLNs are the first sites of immunostimulation. Immunosupression may be the underlying factor for the metastatic involvement of SLNs, which might be secondary to the significantly decreased number of mature dendritic cells in metastatic SLNs compared with tumor-free SLNs.

Functional nuclear medicine imaging of medullary thyroid cancer.

Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts for 3-12% of all thyroid cancers. As opposed to other types of dedifferentiated thyroid tumours, MTC cells are highly functional, producing and secreting high amounts of calcitonin and carcinoembryonic antigen. As parafollicular C cells are of neural crest origin, MTC acts as a neuroendocrine tumour also and expresses somatostatin receptors. Although conventional radiological methods such as ultrasonography, computed tomography and magnetic resonance imaging are widely used in the primary diagnosis and staging, they often fail to localize the residual or recurrent disease because the majority of MTC recurrence presents as occult disease. Thus, owing to functional characteristics of MTC, functional imaging modalities of nuclear medicine play a major role in the diagnostic and therapeutic strategies for MTC. Among nuclear medicine modalities, Tc(V) -dimercaptosuccinic acid, In-octreotide and I/I-meta-iodobenzylguanidine are commonly used in the diagnostic and even more in postoperative work-up of MTC. Alternatively, F-fluorodeoxyglucose and other positron emission tomography radiopharmaceuticals such as F-fluorodopa or F-fluorodopamine as well as radiolabelled antibodies such as Tc/I/I anticarcinoembryonic antigen, antigastrin, and anticholecystokinin-B have promising results. Functional imaging has a great advantage for nuclear medicine techniques in the routine work-up of MTC patients and also has a wide use in experimental studies.

Sentinel lymph node detection in early stage cervical cancer: a prospective study comparing preoperative lymphoscintigraphy, intraoperative gamma probe, and blue dye.

OBJECTIVE: The objective of this prospective study was to determine the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using lymphoscintigraphy (LS), gamma probe, and blue dye. METHODS: A total of 32 patients with early stage cervical cancer (FIGO IA2-IIA) who were treated with total abdominal hysterectomy and bilateral pelvic and paraortic lymphadenectomy underwent SLN biopsy. LS was performed on all the patients following the injection of 74 MBq technetium-99m-nanocolloid pericervically. The first appearing persistent focal accumulation on either dynamic or static images of LS was considered to be an SLN. Blue dye was injected just prior to surgical incision in 16 patients (50%) at the same locations as the radioactive isotope injection. During the operation, blue-stained node(s) were excised as SLNs. For gamma probe, a lymph node was accepted as an SLN, if its ex vivo radioactive counts were at least 10-fold above background radioactivity. SLNs, which were negative by routine hematoxylin and eosin (H&E) examination, were histopathologically reevaluated for the presence of micrometastases by step sectioning and immunohistochemical staining with pancytokeratin. RESULTS: At least one SLN was identified for each patient by gamma probe. Intraoperative gamma probe was the most sensitive method with a technical success rate of SLN detection of 100% (32/32), followed by LS 87.5% (28/32) and blue dye 68.8% (11/16), respectively. The average number of SLNs per patient detected by gamma probe was 2.09 (range 1-5). The localizations of the SLNs were external iliac 47.8%, obturatory 32.8%, common iliac 9%, paraaortic 4.4%, and paracervical 6%. Micrometastases, not detected by routine H&E were found by immunohistochemistry in one patient. On the basis of the histopathological analysis, the negative predictive value for predicting metastases was 100%, and there were no false-negative results. CONCLUSIONS: Preoperative LS with radiocolloids, intraoperative lymphatic mapping with blue dye and gamma probe are all feasible methods comparable with each other for SLN detection in early stage cervical cancer patients, but gamma probe is the most useful method in terms of technical success.

Effects of cavity reconstruction on morbidity and quality of life after canal wall down tympanomastoidectomy.

INTRODUCTION: Canal wall down tympanomastoidectomy is commonly used to treat advanced chronic otitis media or cholesteatoma. The advantages of canal wall down mastoidectomy are excellent exposure for disease eradication and postoperative control of residual disease; its disadvantages include the accumulation of debris requiring life-long otological maintenance and cleaning, continuous ear drainage, fungal cavity infections, and the occurrence of dizziness and vertigo by changing temperature or pressure. OBJECTIVE: To evaluate whether cavity-induced problems can be eliminated and patient comfort can be increased with mastoid cavity reconstruction. METHODS: In total, 11 patients who underwent mastoid cavity reconstruction between March 2013 and June 2013 comprised the study group, and 11 patients who had dry, epithelialized CWD cavities were recruited as the control group. The study examined three parameters: epithelial migration, air caloric testing, and the Glasgow Benefit Inventory. Epithelial migration, air caloric testing, and the Glasgow Benefit Inventory were evaluated in the study and control groups. RESULTS: The epithelial migration rate was significantly faster in study group (1.63±0.5mm/week) than control group (0.94±0.37mm/week) (p=0.003, p<0.05). The mean slow component velocity of nystagmus of the study group (13.33±5.36°/s) was significantly lower when compared to control group (32.11±9.12°/s) (p=0.018). The overall the Glasgow Benefit Inventory score was -7.21, and the general subscale, physical and social health scores were -9.71, -21.09, and +20.35, respectively in the control group. These were +33.93, +35.59, +33.31, and +29.61, respectively in the study group. All but the social health score improved significantly (0.007, 0.008, 0.018, and 0.181, respectively). CONCLUSIONS: Cavity reconstruction improves epithelial migration, normalizes caloric responses and increases the quality of life. Thus, cavity rehabilitation eliminates open-cavity-induced problems by restoring the functional anatomy of the ear.

The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake.

The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on mRNA expressions of Na/I symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSH-R), and radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 microM of 5-Aza, and 1 microM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as the counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-Aza increased TPO mRNA levels 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels, and made no differences on other thyroid specific genes investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important differences in other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both cell lines. Furthermore, in short-term treatment, ATRA repressed NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any differences in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). We have shown an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent.

The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake.

The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on the mRNA expressions of the sodium and iodine (Na/I) symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyroid-stimulating hormone receptor (TSH-R), as well as radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 microM of 5-AZA, and 1 microM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid-stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-AZA increased TPO mRNA levels by 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels and made no change on other thyroid-specific genes that were investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important difference in the other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both the cell lines. Furthermore, in short-term treatment, ATRA repressed the NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any changes in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). In our study, we showed an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent.

Simultaneous surface registration of ictal and interictal SPECT and magnetic resonance images for epilepsy studies.

BACKGROUND: Subtraction of ictal and interictal single photon emission computed tomography (SPECT) images is known to be successful in localizing the seizure focus in the pre-surgical evaluation of patients with partial epilepsy. A computer-aided methods for producing subtraction ictal SPECT co-registered to the magnetic resonance image (MRI) (the SISCOM method) is commonly used. The two registrations involved in SISCOM are (1) between the ictal-interictal SPECT images, which was shown to be the more critical, and (2) between the ictal image and MRI. OBJECTIVE: To improve the accuracy of ictal-interictal registration in SISCOM by registering all three images (ictal, interictal SPECT, MRI) simultaneously. METHODS: The registration problem is formulated as the minimization of a cost function between three surfaces. Then, to achieve a global minimum of this cost function, the Powell algorithm with randomly distributed initial configurations is used. This technique is tested by a realistic simulation study, a phantom study and a patient study. RESULTS: The results of the simulation study demonstrate that, in surface-based registration, the triple-registration method results in a smaller ictal-interictal SPECT registration error than the pair-wise registration method (P<0.05) for a range of values of the cost-function parameter. However, the improved registration error is still larger than that obtained by the normalized mutual information method (P<0.001), which is a voxel-based registration algorithm. The phantom and patient studies reveal no observable difference between registration results. CONCLUSIONS: Although the improved accuracy of triple registration is slightly worse than voxel-based registration, it will soon be possible to apply the results of this study in research utilizing the triple-registration principle to improving voxel-based results of ictal-interictal registration.

In vivo characterisation of parathyroid lesions by use of gamma probe: comparison with ex vivo count method and frozen section results.

OBJECTIVE: In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. STUDY DESIGN AND SETTINGS: Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts relative to postexcision background of the adjacent normal tissue (ex vivo/Bkg). RESULTS: A total of 70 excised lesions were evaluated. In vivo/Bkg counts obtained from parathyroid adenoma were significantly different from parathyroid hyperplasia (z = -3.093, P = 0.002) and other lesions (z = -3.958, P = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate parathyroid adenoma from hyperplasia with a sensitivity, specificity, and accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity, specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%, and 65.9%, respectively. The difference between the accuracy of these 2 tests was not significant statistically (P = 0.137). Sensitivity of frozen section to differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%, respectively. CONCLUSIONS: Patient-specific optimal protocol for timing of sestamibi injection together with in vivo/Bkg method is a useful alternative method in guiding the surgeon to differentiate parathyroid adenoma from parathyroid hyperplasia and other tissues and may help surgeons' decisions during the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more accurate results than frozen section.

Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide synovectomy.

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.

Intra-Arterial Radionuclide Therapies for Liver Tumors.

Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors.

Clinicopathologic and radiopharmacokinetic factors affecting gamma probe-guided parathyroidectomy.

HYPOTHESIS: The kinetics of technetium Tc 99m sestamibi (MIBI) in primary hyperparathyroidism are variable and affected by the cellular size of the abnormal glands, the parathyroid hormone levels, and the functional expression of P-glycoprotein (Pgp). The success of gamma probe-guided parathyroidectomy is closely related to the parathyroid-to-thyroid activity ratio at the time of surgery. Preoperative determination of maximum uptake ratio may improve the surgical outcome. DESIGN: Thirty-one patients with primary hyperparathyroidism attributed to a solitary parathyroid adenoma (27 patients) or multiglandular hyperplasia (4 patients) underwent dynamic MIBI imaging preoperatively. Maximum MIBI activity and activity elimination half-life in the abnormal parathyroid glands and thyroid glands were measured, and the maximum uptake ratio was calculated. After a second MIBI injection on the day of surgery, all patients underwent gamma probe-guided parathyroidectomy and cervical exploration. Timing of surgery after MIBI injection was individualized according to the optimal time to surgery (time to maximum uptake ratio), which was determined by preoperative scintigraphy. During surgery, the gamma probe was used to measure ex vivo counts of excised lesions and adjacent postexcision normal tissue (background). Image characteristics, MIBI kinetics, and gamma probe findings were correlated with gland volume, oxyphil cell content, Pgp expression, and serum parathyroid hormone levels. RESULTS: Probe localization of abnormal glands at maximum uptake ratio was successful in all patients. The volume of the parathyroid lesion ranged from 0.03 to 9.8 mL (median, 0.7 mL). Parathyroid maximum MIBI activity correlated with the volume of the gland (r = 0.54, P = .002) and serum parathyroid hormone level (r = 0.58, P = .001). No correlation between maximum MIBI activity and oxyphil cell content or Pgp expression could be demonstrated. Elimination half-life of MIBI from parathyroid inversely correlated with Pgp (r = -0.36, P = .05). The ex vivo lesion-background count ratio positively correlated with volume of the gland (r = 0.66, P = .001) and parathyroid hormone level (r = 0.48, P = .006). Ex vivo lesion counts and Pgp expression were negatively correlated (r = -0.37, P = .04). CONCLUSIONS: A strong relationship between volume of the parathyroid gland, serum parathyroid hormone levels, and MIBI uptake exists in primary hyperparathyroidism. Gamma probe-guided localization of abnormal gland(s) can be more successful if surgery is undertaken at maximum uptake ratio. High Pgp expression increases MIBI parathyroid clearance rate, decreases gamma probe counts, and may significantly alter the optimal time to surgery.

Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors.

Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T(1/2) =9.5 hr; beta+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was > 95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0 +/- 0.7, 13.2 +/- 2.1 and 9.8 +/- 1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio = 1.64), and high kidney uptake must be eliminated before devising a therapy protocol.