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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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].

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.

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.

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.

[Sentinel lymph node biopsy for breast cancer after neoadjuvant chemotherapy: influence of nodal status before treatment].

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.

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.

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.

Does 99mTc-sestamibi uptake discriminate breast tumors?

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).

Preliminary evaluation of a fuzzy logic-based automatic quantitative analysis in myocardial SPECT.

Unlabelled: This study validates a new quantitative myocardial perfusion SPECT software.

Methods: 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 detection of sentinel lymph node in nuclear medicine].

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.

Single static view 99mTc-sestamibi scintimammography predicts response to neoadjuvant chemotherapy and is related to MDR expression.

We examined the relevance of a pre-treatment single static view 99mTc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations.