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Pain from anticancer drugs-induced neuropathies is difficult to treat and can significantly alter the patient's quality of life. These neuropathies are considered relatively resistant to conventional analgesic drugs (opioids). Opioids are also P-glycoprotein substrates and it has been demonstrated that the P-glycoprotein is linked to the integrity of blood-brain barrier protecting the nervous system. Previous works presented an increase of P-glycoprotein in vincristine- and cisplatin-induced neuropathy which could potentially decrease opioid efficiency. To test this hypothesis, the efflux inhibition of P-glycoprotein and the antinociceptive effect of morphine were assessed in normal and cisplatin-induced neuropathic rats after the administration of the P-glycoprotein inhibitor (R101933). R101933 (20 mg/kg) inhibited significantly the efflux transporter under the condition of the study and had no analgesic effect. Nociceptive thresholds were measured by the paw pressure test. R101933 (20 mg/kg) enhanced antinociceptive activity of morphine (0.5 mg/kg) to a maximum of +58% and +35%, respectively compared with control animals and animals treated by morphine alone (0.5 mg/kg). R101933 increased morphine (2 mg/kg) antinociceptive activity to a maximum of +105% compared with control animals and to a maximum of +41% compared with morphine alone (2 mg/kg). This study demonstrated that cisplatin-induced neuropathy may present a particular pathophysiology with a multidrug resistance, of the central nervous system, to analgesics. This resistance can be blocked by a P-glycoprotein inhibitor which may enhance analgesia of low doses of morphine.

This study assessed the 1H HRMAS NMR spectroscopic profile of articular cartilage in both physiological and osteoarthitic situations. One-dimensional and two-dimensional 1H HRMAS NMR spectra were obtained from the tibial plateau cartilage of healthy and operated (unilateral medial meniscectomy and sham surgery) guinea pigs at different stages of disease, over a 6-month period. The major osteoarthritis-induced 1H HRMAS NMR changes were an increase of the N-acetyl peak of proteoglycans (at day 20 after meniscectomy) and a decrease after day 60 as the pathology evolved. These proteoglycan changes revealed by 1H HRMAS NMR analysis were validated by proteoglycan biochemistry assays. 1H HRMAS NMR analysis also evidenced a sharp increase in methylene resonances of chondrocyte membrane lipids from day 90 as a marker of apoptosis. There was an increase of the mobile methyl group of collagen at day 120, which was associated with collagen breakdown. 1H HRMAS NMR analysis provided a multifactorial and sequential picture of cartilage degradation at the extracellular matrix and chondrocyte levels.

La plupart des programmes de recherche sur les nouveaux radiopharmaceutiques portent actuellement sur les traceurs utilises en tomographie par emission de positons (TEP). Seules quelques equipes continuent a travailler sur des nouveaux traceurs non fluores. Toutefois, l'arrivee des gammas cameras TEMP/TDM et le fremissement des cameras a semi-conducteur, pourraient donner un nouvel elan au developpement des traceurs non TEP. Nous exposons dans cet article l'experience acquise par notre laboratoire dans la conception et l'etude de deux nouvelles familles de molecules non fluorees. Le 99m Tc-NTP 15-5 se lie sur les proteoglycanes et pourrait ainsi etre utilise pour le diagnostic ou suivi de l'arthrose et du chondrosarcome. Les iodobenzamides, traceurs de la melanine, sont actuellement compares au 18 F-fluorodeoxyglucose dans un essai de phase III pour le suivi et le diagnostic de metastases de melanome. Nos derniers travaux portent sur de nouveaux analogues heterocycliques utilisables pour le traitement du melanome.

In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC.Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method.The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy.Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.

Background: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. Methods: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of 99mTc-sestamibi in nervous tissue. Results: Quinidine (30 mg/kg) increased 99mTc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. Conclusion: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity.

Procedure guidelines for scintigraphic detection of sentinel node in breast cancer are presented. The paper was written by several experts in this field on behalf of the European Association of Nuclear Medicine Oncology and Dosimetry committees and approved by the Executive Committee.

Resume Le but de ce travail etait d’evaluer la fixation du 18FDG en TEP dans les lymphomes de Hodgkin en fonction de differents parametres histopathologiques ainsi que l’impact de l’examen sur la stadification et le suivi. Un total de 37 patients a beneficie d’une evaluation TEP-TDM pretherapeutique. La standardized uptake value (SUV) a ete calculee a posteriori. Celle-ci est superieure dans les lymphomes de Hodgkin a cellularite mixte, comparativement aux scleronodulaires. Par ailleurs, l’examen a entraine un changement de stade dans 35 % des cas comparativement a la TDM injectee. La specificite de la TEP-TDM en fin de traitement a ete de 96 % et son exactitude de 93 %, toutes deux significativement superieures a celles retrouvees en TDM.

Resume But Certaines cameras de tomographie par emission de positons (TEP) offrent la possibilite de choisir entre les modes d’acquisition 2D et 3D. Devant l’absence dans la litterature de donnees comparatives, objectives, obtenues dans les conditions de routine clinique entre les deux modes, nous avons realise une etude comparative reposant sur l’appreciation de criteres qualitatifs et quantitatifs. Materiel et methodes Une serie de 33 examens TEP diversifies a ete selectionnee dans la base de donnees du service de medecine nucleaire. Les examens ont ete realises en six a dix pas sur une camera Discovery ST ® (GE Healthcare), en mode 2D ou 3D, selon les criteres habituels du service puis un pas unique a ete a nouveau enregistre sur une zone pathologique en utilisant l’autre mode. Une coupe choisie au milieu de ce pas a ete analysee dans les deux modes (a l’aveugle et dans le desordre) par sept medecins specialistes en medecine nucleaire, en terme de parametres qualitatifs et quantitatifs. Resultats Le mode 2D est significativement plus performant que le mode 3D en ce qui concerne la qualite globale de l’image pour les patients avec un indice de masse corporelle (IMC) > 27,5 ( p = 0,006) et en ce qui concerne le degre de confiance sur la realite des lesions pour un IMC > 25 ( p = 0,01) ; il en est globalement de meme pour les autres parametres qualitatifs. Le nombre moyen de lesions detectees n’est pas affecte par le mode d’acquisition ( p = 0,63), mais il presente une correlation significative avec la qualite de l’image et le degre de confiance ( p = 0,007 et p = 0,013, respectivement). Conclusion Avec la camera TEP-TDM Discovery ST, le mode 2D fournit de meilleurs resultats que le mode 3D chez les patients en surpoids en terme de qualite d’image et de degre de confiance sur la realite des lesions.

The aim of this study was to evaluate an automatic method based on a computed tomography (CT) derived region of interest (ROI) to quantify the mean standardized uptake value (SUVm) of 18 F-fluoro-deoxy-glucose (FDG) in pulmonary lesions detected by positron emission tomography (PET). A total of 164 pairs of slices were selected in a series of PET/CT studies performed in 26 patients presenting lung tumours of various forms and complexities. On each matched CT slice, a ROI was obtained by growth-region segmentation starting from a pixel contained in the tumour. The obtained ROI was then applied to the PET image to calculate SUVm. Results were compared with the conventional manual method using a geometric ROI positioned directly on the PET lesion. The automatic delineation of the tumour from the CT image was successful in 136 sections (83%). The SUVm calculated by the manual and automatic method were respectively (mean±standard deviation) 5.05±2.39 and 6.70±3.18 ( p p

It has recently been suggested that P-glycoprotein is involved in the genesis and the treatment of the neurotoxic adverse events of anticancer drugs, including vincristine. A lower activity of P-glycoprotein in the peripheral nervous system (PNS) than in the central nervous system could contribute to the neurotoxicity of vincristine. Vincristine treatment is responsible for the induction of multidrug resistance (MDR) gene expression and transporter activity, with deleterious consequences, including a potential decrease in the efficiency of opioid analgesics, antidepressants or antiepileptics. Concerning cisplatin, which is also a strong neurotoxic drug but only an multidrug resistance protein 2 (MRP2) substrate, the same assumption could be suggested for MRP2 nervous function. The aim of this study was to assess MDR gene and protein activity in a rat model of cisplatin-induced neuropathy compared with different peripheral nerve injury models, i.e. mononeuropathy and inflammatory pain (monoarthritis). First, in cisplatin-induced neuropathy, this study demonstrated low MRP2 gene expression in dorsal root ganglia compared with the brain and spinal cord, which could contribute to the strong neurotoxicity of cisplatin in the PNS and particularly the dorsal root ganglia. Thus, gene expression increased in cisplatin-induced neuropathy but decreased in mononeuropathy and remained unchanged in monoarthritis models. Transporter activity of nervous tissues increased in the cisplatin-induced neuropathy, mononeuropathy and monoarthritis to different intensities (3.7-, 1.8- and 1.8-fold, respectively). The development of a MDR in the cisplatin-induced neuropathy is a striking difference with mononeuropathy and monoarthritis models, and characterizes the neuropathies induced by this anticancer drug.

Background: The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs). Objectives: It was the aim of this study to assess diagnostic performances of technetium-99m (99mTc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients. Methods: One hundred and eighteen patients presenting with an SPN ≤3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1–4.5 h after injection of 459–770 MBq of 99mTc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology. Results:99mTc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPN ≤1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both 99mTc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively. Conclusions: The diagnostic accuracy of 99mTc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.

This paper presents the first results on a prototype of a large-area X-ray imaging device made out of hybrid CMOS pixel detectors. The challenges of manufacturing and implementing imaging devices on an area larger than the single component size, with a seamless sensitive area, are addressed via a preliminary evaluation of the images. A sensitive area of approximately 6×3 cm 2 was built with eight single ASIC chips performing photon counting and bump-bonded to two high-resistivity p–n silicon sensors working in a reverse bias mode. Each chip consists of 256×256 identical square pixels of 55 μm side. The image delivered is a 1024×512-pixel matrix. Dedicated read-out electronics, software and mechanical supports have been developed. We report and discuss the challenges of the system in terms of the resulting quality of static images obtained with a 70 kV X-ray tube.

Vincristine (VCT) is a neurotoxic agent and also a substrate of multidrug resistance (MDR) transporters such as P-glycoprotein (P-gp) and MDR-associated proteins 1 and 2 (MRP1 and MRP2). These proteins are expressed in the central and peripheral nervous systems (CNS and PNS) and normally protect these structures against the harmful effects of VCT. The aim of this study was to elucidate the paradoxical relation between the MDR transporters and the VCT neurotoxicity. With a validated rat model of VCT-induced neuropathy, (1) the expressions of mdr1a (P-gp), mdr1b (P-gp), mrp1 (MRP1), and mrp2 (MRP2) genes were assessed by quantitative real-time polymerase chain reaction, and (2) the transporter activity was monitored using a radioactive tracer, (99m)Tc-sestamibi, in the CNS and PNS. The results showed higher expression of mdr1a and mdr1b genes (x3 and x35, respectively) in the brain than in the spinal ganglia in both control and treated animals. Transporter activity was higher (x10) in the CNS than in the PNS. Hence, P-gp protection may be lower in the PNS than in the CNS, and this may be responsible for the peripheral neurotoxicity of P-gp substrates. VCT treatment increased expression of the mdr1a gene in the CNS and PNS (both x1.7), mrp1 gene in the PNS (x1.7), and transporter activity in both the CNS and the PNS (x4 and x8, respectively). This transporter induction may induce adverse effects when analgesic drugs are administered to treat neuropathic pain.

The purpose of this study was to assess the value of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) in predicting the evolution of left ventricular volumes in patients treated successfully in the acute phase of a myocardial infarction (MI).Twenty-nine patients with acute MI and early percutaneous transluminal coronary angioplasty (PTCA) were included in this study. A rest Tc-99m sestamibi electrocardiography (ECG)-gated SPECT study was performed 21 +/- 5 days after PTCA. The myocardial perfusion index was calculated by use of a semiautomatic sectorial analysis. All patients had contrast ventriculography performed during the acute phase and 6 months later. The patients were separated into two groups according to the absence (group I, n = 21) or presence (group II, n = 8) of end-systolic enlargement. The perfusion index in the infarct sectors was -2.29 +/- 2.90 SD in group I and -6.40 +/- 2.85 SD in group II ( P.01). With a cutoff value of -2.46 SD, the sensitivity and specificity of Tc-99m sestamibi SPECT for the prediction of end-systolic volume enlargement were 100% and 62%, respectively. When the functional data from ECG-gated acquisitions were added, specificity increased to 86%.Despite successful PTCA in the acute phase of MI, an increase in end-systolic volume was observed at 6 months in 28% of patients. Tc-99m sestamibi ECG-gated SPECT performed 3 weeks after the acute phase could predict this enlargement with a high accuracy.

Aim : Peroperative detection is usually performed with a gamma probe equipped with a single-hole collimator (SHC). The aim of this study was to compare SHC with a new highly resolutive multi-hole collimator (MHC) in situations simulating the in vivo detection of two radioactive sources. Materials and Methods : The probe was composed of a SHC or a MHC, a CsI(Tl) crystal, a photomultiplier tube and a count rate unit. Sensitivity response curves were experimentally obtained with a 57 Co source. From these values, the response curve in front of two small sources was simulated with an Excel software. A 30 MBq source (A) was placed at 1 cm depth and a 300 kBq source (B) was placed, successively, at 1, 3 and 5 cm. B was then moved towards A by 1 mm steps. A threshold background/signal of 50% was used to determine the minimal distance between the sources ( D min ) to remain separately detectable. Results : At 1, 3 and 5 cm depth, D min was, respectively, 35, 45 and 53 mm for SHC and 14, 17 and 20 mm for MHC and the count rate in front of B was, respectively, 3060, 480 and 210 cps with the SHC and 900, 360 and 150 cps with the MHC. Conclusion : When compared with SHC, the loss in sensitivity with the MHC is only moderate for long source–probe distances while the gain in resolution remains important at any distance. MHC is an interesting option for peroperative detection.

Aim : Radioguided Occult Lesion Localization (ROLL) is a method for guiding the excision of occult breast lesions. A radiotracer is injected preoperatively in the tumor. The surgeon can locate the lesion with a gamma probe. It has been recommended that the tissue is resected where the activity falls rapidly. But this cut-off level can fluctuate depending on the user. The aim of this study was to compare the accuracy of two different types of collimation. Materials and methods : To simulate the detection of a radioactive “lesion”, 0.2 ml of a solution of 99mTc labeled colloids (4 MBq) were deposited at 3 cm depth in a chunk of cow muscle. Detection was performed with a gamma probe (GammaSup, Clerad, F) equipped either with a regular or with an additional high-resolution collimator. The response curve was drawn moving laterally the probe on the chunk of cow by 5 mm steps. Edges of resection were determined with different cut-off levels (from 5 to 50% of maximum counts by 5% steps). Results : Without additional collimator, the mean distance between injection point and resection edge was 18 mm, standard deviation 7.8 mm with a range between 11 and 18 mm. With additional collimator, the mean distance decreased to 10 mm (−44%), standard deviation 4.2 mm (−46%) with a range between 6 and 10 mm. Conclusion : The results demonstrate that the additional collimator provides more precise and reproductive delineation of the injection site. It should be optimal for the ROLL technique.

Aim: A Monte Carlo code based on GEANT 3.21 and Linux platform has been developed and adaptated to simulate gamma detectors dedicated to specific scintigraphic applications. Materials and methods: GEANT 3.21 is freely available at the CERN program library. It has been written for simulating the interactions of particles with energy > 10 keV. The energy of the gamma rays used in scintigraphic imaging never exceeds 511 keV. Interaction cross-sections for energies between 10 keV and 10 MeV and three media of interest obtained with this program have been compared with data available on the NIST web site. A gamma peroperative hand-held probe has then been simulated. Sensitivity and spatial resolution were evaluated. Results: The high standard deviation for total attenuation coefficient is 4.7% with an uncertainty around 4% given by NIST. The good results obtained have allowed us to go farther in computer programming. In the hope of integrating all the detection lines new routines have been introduced for the simulation of scintillation photons and optical effects. First simulated optical spots have a diameter of 2.5 mm (FWHM) for a 6 mm NaI(Tl) thickness and gamma rays of 140 keV. Conclusion: The code was recently improved with the implementation of a photomultiplier tube and the algorithm for the image reconstruction. In this way, the computed image can be compared with optical image obtained just before the photocathode to improve algorithm. Soon, simulation results will be tested with a mini gamma-camera prototype.

Aim FBP and OSEM are the most popular tomographic reconstruction methods in scintigraphy. FBP is a simple method but artifacts of reconstruction are generated which corrections induce degradation of the spatial resolution. OSEM takes account of statistical fluctuations but noise strongly increases after a certain number of iterations. We compare a new method of tomographic reconstruction based on discrete geometry (DG TOMO) to FBP and OSEM. Materials and methods Acquisitions were performed on a three-head gamma-camera (Philips) with a NEMA Phantom containing six spheres of sizes from 10 to 37 mm inner diameter, filled with around 325 MBq/l of technetium-99 m. The spheres were positioned in water containing 3 MBq/l of technetium-99 m. Acquisitions were realized during a 180°-rotation around the phantom by 25-s steps. DG TOMO has been developed in our laboratory in order to minimize the number of projections at acquisition. Two tomographic reconstructions utilizing 32 and 16 projections with FBP, OSEM and DG TOMO were performed and transverse slices were compared. Results FBP with 32 projections detects only the activity in the three largest spheres (diameter ⩾22 mm). With 16 projections, the star effect is predominant and the contrast of the third sphere is very low. OSEM with 32 projections provides a better image but the three smallest spheres (diameter ⩽17 mm) are difficult to distinguish. With 16 projections, the three smaller spheres are not detectable. The results of DG TOMO are similar to OSEM. Conclusion Since the parameters of DG TOMO can be further optimized, this method appears as a promising alternative for tomoscintigraphy reconstruction.

Thallium-201 and technetium-99m-MIBI uptake are comparable in "maimed" (i.e., partially viable) and hibernating myocardium. The appreciation of myocardial viability should be based not only on the presence of a regional contractility improvement, but also on the evaluation of the initial level of contractility and of tracer uptake in the concerned area.

Myocardial protection is usually studied in vitro on perfused heart preparations, but never directly on cultured cardiomyocytes. We evaluated a model of cultured newborn rat cardiomyocytes to study both the cytotoxicity and the protective effect against chemical hypoxia of three cardioplegic solutions (St Thomas' I, Bretschneider, St Thomas' II) under normothermic (37°C) and hypothermic (4°C) conditions. Cytotoxicity was evaluated in 50% and 100% concentrations of the cardioplegic solutions with incubation times from 90 to 360 min. Myocardial protection was studied in 50% cardioplegic solution with metabolic inhibitors. Immediate and late viabilities, after 24 h of recovery in the medium, were evaluated by simultaneous staining with fluorescein diacetate and propidium iodide.

A decrease in the intracellular drug concentration in resistant cells as compared to sensitive cells is one of the characteristics of the MDR phenotype. P-glycoprotein (Pgp) is thought to be responsible for an active efflux of some lipophilic drugs such as anthracyclines. Anthracyclines such as daunomycin are highly effective anticancer agents but induce a well-described, while incompletely explained, cardiac toxicity. In this study, we investigated the MDR phenotype in rat myocardium in terms of gene expression, detection of Pgp and indirect evaluation of Pgp function. A clear mdr1a gene specific expression in rat cultured myocardial cells and cardiac tissue was detected by RT-PCR. The incorporation of [3H]daunomycin in myocardial cell cultures was studied with and without reversing agents. Daunomycin was found to have a high accumulation in cardiac cells illustrated by a Ci/Ce ratio of 2890. This high accumulation was moderately but significantly (p < 0.05) increased in the presence of a MDR reversing agent such as verapamil, PSC 833 or S9788. These results suggest that blockade of the Pgp in humans may result in an increased toxicity of several Pgp substrates in normal tissues like the myocardium.

This study on a rat model of grade II chondrosarcoma aimed to determine whether the radiotracer N-(triethylammonium)-3-propyl-[15]ane-N5 radiolabeled with 99mTc (99mTc-NTP 15-5), which binds to cartilage proteoglycans, has pathophysiologic validity for in vivo imaging of cartilage tumoral tissue. Methods: We used 2 experimental approaches with the Swarm chondrosarcoma rat model: that is, a primary paratibial location and local recurrence after intralesional curettage. 99mTc-NTP 15-5 scintigraphy and 99mTc-hydroxymethylenediphosphonate (99mTc-HMDP) scanning were performed at regular intervals during 50 d after tumor implantation in a paratibial location (primary model; n = 12 animals) and after intralesional curettage in a femoral condyle location (recurrence model; n = 9 animals). For each animal, positive scans were analyzed at each time point using the target-to-background ratio (TBR), with the target region of interest delineated over the tumor and the background region of interest over muscle. In each model, the TBR time course was followed against primary tumoral growth or recurrence. Tumor volume was monitored for 2 mo by measuring the 2 perpendicular diameters. At study end, animals were sacrificed for histopathologic analysis. Results: For both models, 99mTc-NTP 15-5 scans showed tracer accumulation at the site of implantation or curettage. For the primary tumor model, the mean TBR was 1.6 ± 0.14 by day 4 after implantation and increased over time as the disease progressed, with a mean TBR of 4.25 ± 0.25 on day 45. For the recurrence model, mean TBR was 3.27 ± 0.24 by day 4 after curettage and increased with recurrence, with a mean value of 5.25 ± 0.49 on day 50. 99mTc-HMDP bone scans were negative for both models throughout the study; at a later stage of the study, an area of 99mTc-HMDP accumulation was seen in the diaphysis of the bone adjacent to the tumor and was attributed to remodeling. Conclusion: These experimental results in 2 preclinical models of grade II chondrosarcoma bring forward data in favor of 99mTc-NTP 15-5 radiotracer for imaging primary growth of chondrosarcoma and its local recurrence after surgery.

Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters.This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 +/- 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging.Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.

In recent years, there has been dramatic worldwide increase in incidence of malignant melanoma. Although localised disease is often curable by surgical excision, metastatic melanoma is inherently resistant to most treatments. In this context, targeted radionuclide therapy could be an efficient alternative. After pharmacomodulation study, we selected a quinoxaline derivative molecule (ICF01012) for its high, specific and long-lasting uptake in melanoma with rapid clearance from nontarget organs providing suitable dosimetry parameters for targeted radiotherapy. Aim of this study was to investigate, in vivo, efficacy of [131I]ICF01012 on nonmetastatic B16F0, metastatic B16Bl6 or human M4Beu melanoma tumours. First, colocalisation of ICF01012 with melanin by SIMS imaging was observed. Second, we showed that treatment drastically inhibited growth of B16F0, B16Bl6 and M4beu tumours whereas [ 131 I]NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis and measure of PCNA proliferation marker expression showed that residual B16 tumour cells exhibit a significant loss of aggressiveness after treatment. This effect is associated with a lengthening of the treated-mice survival time. Moreover, with B16Bl6 model, 55% of the untreated mice had lung metastases whereas no metastasis was counted on treated group. Our data demonstrated a strong anti-tumoural effect of [131I]ICF01012 for radionuclide therapy on murine and human in vivo pigmented melanoma models, whatever their dissemination profiles and their melanin content be. Further studies will attempt to optimise therapy protocol by increasing the balance between the anti-tumoural effect and the safety on nontarget organs. ' 2009 UICC

Background Thrombus aspiration devices have been shown to improve reperfusion criteria and to reduce distal embolization in patients treated by percutaneous coronary interventions (PCI) in the acute phase of ST-elevation myocardial infarction (STEMI). There are, however, little data about their efficacy in the reduction of infarct size. Methods We sought to assess in a prospective randomized trial the impact of thrombus aspiration on infarct size and severity and on left ventricular function in high-risk patients with a first STEMI. The primary end point was scintigraphic infarct size, and secondary end points were infarct severity and regional and global left ventricular function. Forty-four patients with completely occluded (Thrombolysis in Myocardial Infarction flow 0-1) proximal segments of infarct-related artery were randomly assigned to thrombus aspiration group with the Export catheter (n = 20) (Medtronic, Inc, Minneapolis, MN) or PCI-only group. A rest Tc-99-mibi gated single-photon emission computed tomographic and contrast-enhanced magnetic resonance imaging were performed 6 ± 2 days later. Results Infarct size was comparable in patients in the thrombus aspiration group and PCI-only group (30.6% ± 15.8% vs 28.5% ± 17.9% of the left ventricle, P = .7) as was infarct severity in infarct-related artery territory (55% ± 12% vs 55% ± 14%, P = .9). Transmurality score as assessed by magnetic resonance imaging was similar in both groups (2.03 ± 1.05 vs 2.16 ± 1.21, P = .7). There was no impact of thrombus aspiration on other secondary end points. Conclusion In our study, thrombus aspiration with the Export catheter performed as adjunctive therapy in high-risk patients with total occlusion of the proximal part of major coronary arteries does not decrease infarct size or severity and has no effect on left ventricular regional and global function.

This study aimed to report the first single-photon emission computed tomographic (SPECT) imaging of articular cartilage in mice using 99mTc-NTP 15-5 radiotracer. Mice intravenously injected with 99mTc-NTP 15-5 were submitted to (1) dynamic planar imaging, (2) static planar imaging, (3) 1 mm pinhole SPECT acquisition, and (4) dissection. Tomographic reconstruction of SPECT data was performed with a three-dimensional ordered subset expectation maximization algorithm, and slices were reconstructed in three axes. 99mTc-NTP 15-5 rapidly accumulated in the joint, with a peak of radioactivity being reached from 5 minutes postinjection and maintained for at least 90 minutes. Given that bone and muscle did not show any accumulation of the tracer, highly contrasted joint imaging was obtained from 15 minutes postinjection. When 1 mm pinhole SPECT acquisition was focused on the knee, the medial and lateral compartments of both the femoral condyle and tibial plateau were highly delineated, allowing a separate quantitation of tracer accumulation within each component of the femorotibial joint. A good correlation was found between tracer uptake determined by region of interest analysis of both planar and SPECT scans and dissection. This new approach to imaging of cartilage in mice provides joint functionality assessment in vivo, giving a unique opportunity to achieve a greater understanding of cartilage physiology in health and disease.

Studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer. Some SLN-positive patients have low risk of nonsentinel lymph node (non-SLN) involvement. Our goal was to determine clinicopathological factors correlating with the presence of non-SLN metastases in patients after NAC and to assess the validity of nomograms predicting additional axillary metastases.Patients with infiltrating breast carcinoma (n = 132) were studied prospectively. All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Lymphatic mapping was done using the isotope method. Fifty-one patients were SLN positive.In univariate analysis, tumor size (P = 0.016) and the size of SLN metastases (P = 0.0055) were significantly correlated with the presence of non-SLN metastases. In multivariate analysis, SLN macrometastases (P = 0.047) conferred significantly increased risk of non-SLN metastases. The Memorial Sloan-Kettering Cancer Center nomogram was not reliably predictive for non-SLN metastases (area under the receiver operating characteristic curve, AUC, of 0.542), whereas the MD Anderson (AUC 0.716) and Tenon scoring systems (AUC 0.778) were validated.Our results suggest that clinicopathological factors predicting non-SLN involvement in SLN-positive patients with and without NAC are essentially the same. The risk of involvement may be assessed using existing nomograms, but additional large prospective studies are needed to determine their accuracy in patients after NAC.

To identify proteins involved in melanoma metastasis mechanisms, comparative proteomic studies were undertaken on B16F10 and B16Bl6 melanoma cell lines and their subsequent syngenic primary tumours as pulmonary metastases were present only in the mice bearing a B16Bl6 tumour. 2DE analyses followed by MALDI-TOF identification showed variations of 6 proteins in vitro and 13 proteins in vivo. Differential expressed proteins in tumours were related to energy production and storage. Two differentially expressed proteins which had not been previously associated to melanoma progression, annexin A1 (ANXA1) and creatine kinase B (CKB), were found both in cells and in tumours. To characterize ANXA1 involvement in melanoma B16 dissemination, we reduced ANXA1 protein level by siRNA and observed a significant decrease of B16Bl6 cell invasion through Matrigel coated chambers. We further demonstrated that the presence of several formyl peptide receptors (FPR1, FPRrs1 and 2) revealed by qRT-PCR, played a role in B16 invasion: incubation of B16Bl6 cells with the FPR agonist (fMLP) or antagonist (tBOC) enhanced or decreased Matrigel coated chamber invasion respectively, with a correlation of ANXA1 levels in both treatments. As ANXA1 could bind to FPRs, this should amplify invasion and enhance melanoma dissemination.

This study aimed to report the first single-photon emission computed tomographic (SPECT) imaging of articular cartilage in mice using 99mTc-NTP 15-5 radiotracer. Mice intravenously injected with 99mTc-NTP 15-5 were submitted to (1) dynamic planar imaging, (2) static planar imaging, (3) 1 mm pinhole SPECT acquisition, and (4) dissection. Tomographic reconstruction of SPECT data was performed with a three-dimensional ordered subset expectation maximization algorithm, and slices were reconstructed in three axes. 99mTc-NTP 15-5 rapidly accumulated in the joint, with a peak of radioactivity being reached from 5 minutes postinjection and maintained for at least 90 minutes. Given that bone and muscle did not show any accumulation of the tracer, highly contrasted joint imaging was obtained from 15 minutes postinjection. When 1 mm pinhole SPECT acquisition was focused on the knee, the medial and lateral compartments of both the femoral condyle and tibial plateau were highly delineated, allowing a separate quantitation of tracer accumulation within each component of the femorotibial joint. A good correlation was found between tracer uptake determined by region of interest analysis of both planar and SPECT scans and dissection. This new approach to imaging of cartilage in mice provides joint functionality assessment in vivo, giving a unique opportunity to achieve a greater understanding of cartilage physiology in health and disease.

In comparison with conventional imaging, nuclear medicine offers an original metabolic approach for the assessment of the therapeutic response. Gallium 67, thallium 201, technetium 99m-labeled sestamibi and diphosphonates can be performed for therapeutic response assessment in lymphoma, brain and breast tumours, sarcoma, or bone metastasis. PET-CT facilities are now easily available in France and are ready to provide a new and accurate tool in oncology, specially for therapeutic evaluation. The procedure consists in the injection of fluor-18-fluoro-déoxyglucose (18FDG), an analogue of glucose, followed by a PET then a CT acquisition for FDG uptake abnormalities location. Therapeutic response is assessed by a decrease of 18FDG tumoral uptake between two consecutive studies. Methodology and interpretation criteria have been recently defined in international guidelines. 18FDG-PET-CT seems to be a valuable tool for therapeutic response assessment of patients with Hodgkin or non Hodgkin malignant lymphoma. Promising preliminary results have been recently published for lung, gastro-intestinal and head and neck cancers. PET-CT could also be able to predict the therapeutic response after the first courses of chemotherapy, allowing an early treatment optimization. Finally, new PET agents pave the way for molecular imaging with promising results in gene therapy and targeted treatment in oncology.

To determine feasibility and accuracy of SLN biopsy in locally advanced breast cancer treated by neoadjuvant chemotherapy.From April 2001 to December 2004, a prospective series was constituted of 74 women with invasive breast carcinoma T1T2T3N0N1 receiving neoadjuvant chemotherapy. The SLN located was removed using subdermal periareolar injection of radiolabelled nanocolloid and axillary lymph node dissection was systematically performed.A SLN was identified in 68/74 (92%) patients. It was metastatic in 30/68 cases (44%). The false negative (FN) rate was 14% (5/35). In the subgroup of 42 patients clinically N(0) before chemotherapy, accuracy was 100 %, and FN rate 0%, in the 32 N1, accuracy was 83%, and FN rate 25%.SLN biopsy using a single subdermal injection of radiolabelled nanocolloid in patients with a breast cancer treated by neoadjuvant chemotherapy is technically feasible and appears to be highly accurate in the subgroup of patients with a clinically negative axilla breast cancer before treatment.

The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs).It was the aim of this study to assess diagnostic performances of technetium-99m ((99m)Tc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients.One hundred and eighteen patients presenting with an SPNor =3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1-4.5 h after injection of 459-770 MBq of (99m)Tc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology.(99m)Tc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPNor =1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both (99m)Tc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively.The diagnostic accuracy of (99m)Tc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.

Our aim is to develop an objective and reproducible kidney volume estimation using SPECT for 9gm Tc-OMSA renal imaging. For this, the major problem stems from the delineation of kidney b orders. Therefore, we used and compared three methods of segmentation : with fixed threshold, g ray level histogram and mathematical morphology technics. The first method applied to a series of patients showed a good correlation w ith kidney diameter measurements from the ultrasound. But this solution i s not operator independent and the research with the phantoms permits thecomparison with t he two other methods which appear much better.

The aim of this work was to investigate 99mTc-sestamibi uptake and histopathological characteristics of breast tumors. Static 99mTc-sestamibi scintimammography (SMM) has been performed in 101 breast tumors (98 patients). SMM were scored from 0 to 4 according to intensity of 99mTc-sestamibi uptake and classified in two groups: SMM with absence or low tumor uptake (0, 1, 2) and SMM with high tumor uptake (3, 4). Tumor histopathological characteristics have been determined on core or excisional biopsy. The 99mTc-sestamibi uptake (low vs. high) correlated to classical prognostic factors: positively with Scarff-Bloom and Richardson (SBR) grade (p0.0005), axillary involvement (p0.0005), and tumor size (p0.0005) and negatively with estrogen receptors (p0.001). Fixation of 99mTc-sestamibi in invasive lobular carcinoma was lower than in invasive ductal carcinoma (p0.01) despite a similar mean tumor size (28 +/- 14 mm vs. 24 +/- 14 mm). Relations between 99mTc-sestamibi uptake and tumor size, histologic type, and axillary involvement were independent variables also significant in multivariate analysis (p0.0005, p0.005, p0.05, respectively). Moreover, the five-year survival rate was higher when 99mTc-sestamibi breast tumor uptake was low (p0.005). This difference is also significant using the Cox model (p0.05). Uptake of 99mTc-sestamibi (low vs. high) discriminates breast tumors with different histopathological characteristics and prognosis.

This study validates a new quantitative myocardial perfusion SPECT software.The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography.The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively.The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.

An automatic method is described for the objective and reproducible alignment of thallium-201 tomoscintigraphic views. Image preparation, polar conversion, and curve analysis are discussed. The method was used for 50 patients with cardiac disease. In all patients a proper reorientation was obtained, although less satisfactory results were observed in patients with septal abnormalities. >

The isotopic detection of the sentinel node is undergoing a fast development in breast cancer and melanoma. It requires a good collaboration between a surgeon and a nuclear medicine specialist. Although the method is now well defined for melanoma, several options remain possible for breast cancer. The injected dose and volume can differ between centers, as well as the sites of injection in terms of their number, anatomical location and depth. However, since all options seem to provide equivalent results, a single intradermal periareolar injection could be the preferred choice. The role of imaging remains controversial, but it provides a definite complementary information, in particular in case of an unusual location of the sentinel node. The addition of dye injection also adds to the results. The optimal use of a peroperative hand-held gamma probe requires some training for the surgeon. A good selection of the indications is essential for a successful detection. Other fields of application are under investigation such as colon cancer, head and neck tumors, lung and prostate cancers. By avoiding a majority of the routine axillary lymph nodes dissections in small breast cancer, the isotopic detection of the sentinel node should dramatically decrease the morbidity of axillary staging and the duration of hospital stay for the patients.

The aim of the trial was to determine the diagnostic accuracy of scintimmammography with technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) in the detection of primary breast cancer and to verify its clinical usefulness. A total of 246 patients with a suspicious breast mass or positive mammogram were included in this prospective European multicentre trial. At 5 min and 60 min (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min p.i. one anterior image was acquired for 10 min. There were 253 lesions (195 palpable and 58 non-palpable), in respect of which histology revealed 165 cancers and 88 benign lesions. Institutional and blinded read results were correlated to core laboratory histopathology results obtained during excisional biopsy. Diagnostic accuracy for the detection of breast cancer was calculated per lesion. The overall sensitivity and specificity of blinded read scintimammography were 71% and 69%, respectively. For palpable lesions, the sensitivity of blinded read and institutional read scintimammography was 83% and 91%, respectively. Sensitivity was not dependent on the density of the breast tissue. Invasive ductal and invasive lobular cancers showed similar sensitivity. The sensitivity and specificity of mammography were 91% and 42%, respectively, and did not depend on the tumour size. In 60% of false-negative mammograms, 99mTc-MIBI was able to diagnose malignancy (true-positive). High-quality imaging with 99mTc-MIBI has a high diagnostic accuracy for the detection of primary breast cancer. Used as a complementary method, scintimammography with 99mTc-MIBI can help to diagnose breast cancer at an earlier stage in patients with dense breasts.

To the Editor: A 77-year-old man was referred because of a 2-year history of asthenia and weight loss with lymphadenopathy. Six months earlier, the patient had been investigated by computed tomogra...

Technetium-99m-sestamibi scintigraphy has recently emerged as a new procedure for the imaging of malignant breast tumors. A large clinical experience has now been collected and this article reviews the main published results. The major drawback of the procedure appears to be its low sensitivity in detecting lesions smaller than 1 cm. The biological background underlying the tracer accumulation is also described. The stimulating potent applications of this functional imaging technique to non-invasively explore the development, and possibly the reversal, of a multidrug resistance under chemotherapy are discussed. The data related to the use of the positron emitter fluor-18-labeled fluorodeoxyglucose (FDG), a very promising agent for imaging breast as well as other solid tumors, are also reviewed. The situation of specific agents, still under development and such as labeled receptor ligands, is examined.

Defect quantification is an important topic in myocardial SPECT. It can be achieved properly only with an automatic and reproducible processing. We propose a new approach lying on the application of discrete geometry and of two aspects of mathematical morphology, namely, skeletonization and segmentation. The properties of the skeleton are essential for carrying out segmentation, which uses many sights of uncertain's theory (fuzzy logic). We present the basis of this application with an in-depth analysis of various methods of skeletonization.

99mTc-labeled tetrofosmin is a new myocardial imaging agent that gives stable heart uptake. However, little is known about the mechanism of uptake in heart tissue. The aim of this study was to assess the factors responsible for the uptake and retention of 99mTc-labeled tetrofosmin in isolated heart mitochondria.Mitochondria were isolated from adult rat heart tissue with competent metabolic function (i.e., respiratory control ratio of 3 and adenosine diphosphate/oxygen ratio of 2) for succinate oxidation. Intramitochondrial volume measured by the distribution of 3H-water and 14C-sucrose was 1.16 +/- 0.23 microliters/mg protein (mean +/- SD). In the isolated mitochondria, uptake could be demonstrated within 30 seconds of addition of oxidative substrate, but adenosine triphosphate alone did not stimulate marked uptake. Uptake was proportional to the amount of mitochondrial protein over a range of 0.2 to 3 mg protein but independent of Tc-labeled tetrofosmin concentration over a range of 0.4 to 200 pmol/L (0.1 to 50 microCi/ml). The presence of Tc-labeled tetrofosmin had no effect on the oxidative capability of the mitochondria. Use of the mitochondrial uncoupler 2,4-dinitrophenol caused release of 92% of radioactivity. Addition of Ca2+ to the mitochondria to partially depolarize the membrane resulted in partial release of activity. Application of the Nernst equation to the uptake data gave rise to a value of -163 mV for the mitochondrial membrane potential.It was concluded that the accumulation of 99mTc-labeled tetrofosmin by the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential.

The myocardial uptake of rest-injected technetium 99m sestamibi on single-photon-emission computed tomographic images was assessed in 25 patients. All had an area of myocardial dysfunction that could be related to a coronary artery stenosis. None of the patients had clinical evidence of a myocardial infarction. Three months after revascularization, viability was demonstrated by contrast angiography and center-line analysis in 21 (78%) of the 27 formerly hibernating territories. Among these, none had a transmural defect, and 38% had a normal technetium 99m-sestamibi uptake. The four transmural preoperative defects were located in territories without viability. Eight of the 9 territories that were normal at scintigraphy proved to be viable postoperatively. It is concluded that as long as some residual technetium 99m-sestamibi uptake is present, viable myocardium is also present.

Exercise thallium-201 single photon emission computed tomography images were compared prospectively with 4-hour redistribution images, with 4-hour reinjection images, and with images obtained at rest on a separate day in 37 patients with documented coronary artery disease. Exercise images were abnormal in 35 patients (95%). On the basis of an improvement in thallium-201 distribution between exercise and nonexercise images, overall sensitivity for the detection of coronary artery stenosis was significantly higher with reinjection at 4 hours (p0.05) or with a rest injection on a separate day (p0.05) than with redistribution imaging (84%, 83%, and 70%, respectively). Reinjection and rest injection were positive more frequently in patients with a wall-motion abnormality (76% and 80%, respectively, vs 64% at redistribution; p0.05 for both) or with90% stenosis (77% and 76%, respectively, vs 58% at redistribution; p0.05 for both). Among the 11 patients who had no evidence of redistribution at 4 hours, five (45%) demonstrated ischemia with reinjection and five demonstrated ischemia in the separate rest study; a total of seven patients showed improvement either at reinjection or rest. Among these 86% had a wall-motion abnormality associated with stenosis of90%, whereas in the other 30 patients these two conditions were observed concomitantly in only 43%. This study demonstrates that the thallium-201 4-hour postexercise reinjection technique is as sensitive as the 2-day rest/exercise method for the detection of coronary artery stenosis and provides additional information when a severe stenosis is associated with a wall-motion abnormality.

A new method for centering and reorienting automatically the left ventricle in thallium-201 myocardial single photon emission computed tomography (SPET) is proposed. The processing involves the following steps: (a) the transverse sections of the left ventricle are segmented, (b) the three-dimensional skeleton of the left ventricle is extracted using tools of mathematical morphology, (c) the skeleton is fitted to a quadratic surface by the least-squares method, (d) the left ventricle is reoriented and centered using the long axis and the coordinates of the centre of the quadratic surface. A series of 30 consecutive exercise and redistribution 201Tl SPET studies were centered and reoriented by two operators twice with this method, and twice manually. There was no significant difference in the mean realignment performed by the automatic and the manual methods while centering differed moderately in some instances. In all cases and for all parameters, the reproducibility of the automatic method was 1.00, while it ranged between 0.74 and 0.98 with the manual centering and reorientation. This automatic approach provides a fast and highly reproducible method for the reconstruction of short- and long-axis sections of the left ventricle in 201Tl SPET.