The use of [(125)I] scintigraphic in vivo imaging in melanoma-bearing mice for a rapid prescreening of vectors to melanoma tissue.

INTRODUCTION: The use of radiolabeled molecules allows the study of in vivo biodistribution, target organs, and kinetic profile after systemic administration by 1) radioactive organ counting and 2) quantitative autoradiographic analysis of whole-body slices (WBA). However, these techniques are time- and animal consuming for several times studied. So, in vivo scintigraphic imaging should appear of interest for a first screening of compounds, as it is able to rapidly demonstrate tumoral uptake and kinetics by serial examinations in the same mice. MATERIALS AND METHODS: In this study, the tumoral distribution and kinetics of six molecules considered as potential melanoma tracers radiolabeled with (125)I were analyzed by gamma-scintigraphy comparatively to the results obtained by WBA. Tumoral uptake has been quantified and expressed by: 1) tumor-to-background ratios and 2) standardized tumoral uptake (STU) in percent injected dose per gram, with tumor weight being extrapolated from the measurement of the two diameters. RESULTS: Results from STU analysis showed good agreement (correlation coefficient = 0.92) with those of WBA, and the same classification of compounds (on the basis of their melanoma affinity) was obtained, with two compounds (of six) being rejected. CONCLUSIONS: [(125)I] scintigraphic imaging appeared as a relevant, easy-going method for a first pharmacologic selection in mice.

Increase in morphine antinociceptive activity by a P-glycoprotein inhibitor in cisplatin-induced neuropathy.

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.

First preclinical imaging of primary cartilage neoplasm and its local recurrence using 99mTc-NTP 15-5 radiotracer.

UNLABELLED: 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 (99m)Tc ((99m)Tc-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. (99m)Tc-NTP 15-5 scintigraphy and (99m)Tc-hydroxymethylenediphosphonate ((99m)Tc-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, (99m)Tc-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. (99m)Tc-HMDP bone scans were negative for both models throughout the study; at a later stage of the study, an area of (99m)Tc-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 (99m)Tc-NTP 15-5 radiotracer for imaging primary growth of chondrosarcoma and its local recurrence after surgery.

Rest and low-dose dobutamine Tc-99m-mibi gated-SPECT for early prediction of left ventricular remodeling after a first reperfused myocardial infarction.

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Targeted radionuclide therapy of melanoma: anti-tumoural efficacy studies of a new 131I labelled potential agent.

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 [(131)I]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 [(131)I]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 non-target organs.

Longitudinal profiling of articular cartilage degradation in osteoarthritis by high-resolution magic angle spinning 1H NMR spectroscopy: experimental study in the meniscectomized guinea pig model.

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.

Effect of thrombus aspiration on infarct size and left ventricular function in high-risk patients with acute myocardial infarction treated by percutaneous coronary intervention. Results of a prospective controlled pilot study.

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.

Proteomic studies of B16 lines: involvement of annexin A1 in melanoma dissemination.

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.

Vincristine-induced neuropathy in the rat is not modified by drug-drug interactions with the P-glycoprotein inhibitor verapamil.

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 (99m)Tc-sestamibi in nervous tissue. RESULTS: Quinidine (30 mg/kg) increased (99m)Tc-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.

Design, synthesis and preliminary biological evaluation of acridine compounds as potential agents for a combined targeted chemo-radionuclide therapy approach to melanoma.

Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy.

Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma.

Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with (125)I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [ (125)I] 5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.

First In Vivo SPECT Imaging of Mouse Femorotibial Cartilage Using 99mTc-NTP 15-5.

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.

Sentinel node in breast cancer procedural guidelines.

Procedure guidelines for scintigraphic detection of sentinel node in breast cancer are presented.

[Evaluation of the therapeutic response: role of isotopic imaging]. / Evaluation de la réponse thérapeutique en cancérologie: place de l'imagerie isotopique.

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.

Involvement of the multidrug resistance transporters in cisplatin-induced neuropathy in rats. Comparison with the chronic constriction injury model and monoarthritic rats.

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.

The solitary pulmonary nodule--is it malignant or benign? Diagnostic performance of Tc-depreotide SPECT.

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 ((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. METHODS: One hundred and eighteen patients presenting with an SPN < or =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. RESULTS: (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 SPN < or =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. CONCLUSIONS: The diagnostic accuracy of (99m)Tc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.

[Sentinel lymph node biopsy for breast cancer after neoadjuvant chemotherapy: influence of nodal status before treatment]. / Lymphadénectomie axillaire sentinelle après chimiothérapie néoadjuvante pour cancer du sein: influence du statut ganglionnaire initial.

OBJECTIVES: To determine feasibility and accuracy of SLN biopsy in locally advanced breast cancer treated by neoadjuvant chemotherapy. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Patterns of P-glycoprotein activity in the nervous system during vincristine-induced neuropathy in rats.

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.

Influence of infarct-zone viability detected by rest Tc-99m sestamibi gated SPECT on left ventricular remodeling after acute myocardial infarction treated by percutaneous transluminal coronary angioplasty in the acute phase.

BACKGROUND: 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). METHODS AND RESULTS: 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%. CONCLUSIONS: 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.