The aim of this analysis was to investigate whether the standardized uptake value (SUV) normalized by lean body mass (SUL) is a more appropriate quantitative parameter compared to the commonly used ...SUV normalized by patient's weight in
Ga-PSMA11 PET/CT.
Ga-PSMA11 PET/CT scans of 121 patients with prostate cancer from two institutions were evaluated. Liver SUV was measured within a 3-cm volume-of-interest (VOI) in the right hepatic lobe and corrected for lean body mass using the Janmahasatian formula. SUV and SUL repeatability between baseline and follow-up scans of the same patients were assessed.
SUV was significantly positively correlated with body weight (r = 0.35, p = 0.02). In contrast, SUL was not correlated with body weight (r = 0.23, p = 0.07). No significant differences were found between baseline and follow-up scan (p = 0.52).
The Janmahasatian formula annuls the positive correlations between SUV and body weight, suggesting that SUL is preferable to SUV for quantitative analyses of
Ga-PSMA11 PET/CT scans.
The alpha(v)beta3 integrin plays an important role in metastasis and tumor-induced angiogenesis. Targeting with radiolabeled ligands of the alpha(v)beta3 integrin may provide information about the ...receptor status and enable specific therapeutic planning. Previous studies from our group resulted in tracers that showed alpha(v)beta3-selective tumor uptake. However, these first-generation compounds predominantly revealed hepatobiliary excretion with high radioactivity found in the liver. In this report, the synthesis and biological evaluation of the first glycosylated RGD-containing peptide (RGD-peptide) for the noninvasive imaging of alpha(v)beta3 expression are described.
Peptides were assembled on a solid support using fluorenylmethoxycarbonyl-coupling protocols. The precursor cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP1 was synthesized by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-beta-D-glycero-D-gulo-heptonic acid (SAA(Bn3)) with cyclo(-Arg(Mtr)-Gly-Asp(OtBu)-D-Tyr(tBu)-Lys-) and subsequent removal of the protection groups. Iodine labeling was performed by the Iodo-Gen method (radiochemical yield > 50%). The in vitro binding assays were performed using purified immobilized alpha(IIb)beta3, alpha(v)beta5, and alpha(v)beta3 integrins. For in vivo experiments, nude mice bearing xenotransplanted melanomas and mice with osteosarcomas were used.
The glycosylated peptide 3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP2 showed high affinity and selectivity for alpha(v)beta3 in vitro (50% inhibitory concentration = 40 nmol/L). Pretreatment studies indicate specific binding of 125IGP2 on alpha(v)beta3-expressing tumors in vivo. Comparison of the pharmacokinetics of 125IGP2 and 125I-3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) 125IP2 revealed for 125IGP2 an increased activity concentration in the blood (e.g., 3.59 +/- 0.35 percentage injected dose %ID/g vs. 1.72 +/- 0.44 %ID/g at 10 min postinjection) and a significantly reduced uptake in the liver (e.g., 2.59 +/- 0.24 %ID/g vs. 21.96 +/- 2.78 %ID/g at 10 min postinjection). Furthermore, a clearly increased activity accumulation in the tumor was found (e.g., 3.05 +/- 0.31 %ID/g vs. 0.92 +/- 0.16 %ID/g at 240 min postinjection), which remained almost constant between 60 and 240 min postinjection. This resulted in good tumor-to-organ ratios for the glycosylated tracer (e.g., 240-min postinjection osteosarcoma model: tumor-to-blood = 16; tumor-to-muscle = 7; tumor-to-liver = 2.5), which were confirmed by the first gamma-camera images of osteosarcoma-bearing mice at 240 min postinjection.
This study demonstrates that the introduction of a sugar moiety improves the pharmakokinetic behavior of a hydrophobic peptide-based tracer. Additionally, this alpha(v)beta3-selective glycosylated radioiodinated second-generation tracer GP2 shows high tumor uptake and good tumor-to-organ ratios that allow noninvasive visualization of alpha(v)beta3-expressing tumors and monitoring therapy with alpha(v)beta3 antagonists. Finally, the favorable biokinetics make the glycosylated RGD-peptide a promising lead structure for tracers to quantify the alpha(v)beta3 expression using PET.
Multicomponent Passerini and Ugi reactions enable the fast and efficient synthesis of redox-active multifunctional selenium and tellurium compounds, of which some show considerable cytotoxicity ...against specific cancer cells.
Nanocrystalline Fe
90
Ni
10
alloys were synthesized by mechanical alloying, starting from a powder mixture of elemental Fe and Ni. The phase evolution and magnetic properties were investigated, as a ...function of milling time, using the X-ray diffraction (XRD), the vibrating sample magnetometer (VSM), and the
57
Fe Mössbauer spectroscopy. From XRD results, we concluded the formation, after 13 h of milling, of a disordered phase
α
-Fe(Ni) (bcc). It has been shown that the increase of milling time decreases the crystallites size and increases the microstrains and the lattice parameter. When the crystallites size decreases, the coercive field,
H
c
, decreases first, then increases and finally reaches a constant value of about 26 Oe. During the periode of the alloy formation, the saturation magnetization,
M
s
, increases with decreasing crystallite size and reaches the highest value of 212 emu/g after 27 h of milling, then,
M
s
remains constant up to 48 h of milling. The adjustment of Mössbauer spectra revealed that the fraction of the (bcc)
α
-Fe(Ni) phase increased with milling time. After 13 h of milling, only the (bcc)
α
-Fe(Ni) phase is observed.
The integrin alphavbeta3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being ...studied to enable noninvasive determination of alphavbeta3 expression. We developed (18)FGalacto-RGD, a (18)F-labeled glycosylated alphavbeta3 antagonist, allowing monitoring of alphavbeta3 expression with positron emission tomography (PET).
Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of (18)FGalacto-RGD in the tumor correlates with alphavbeta3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize alphavbeta3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that (18)FGalacto-RGD with PET enables noninvasive quantitative assessment of the alphavbeta3 expression pattern on tumor and endothelial cells in patients with malignant tumors.
Molecular imaging with (18)FGalacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the alphavbeta3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.
•Stimulus-evoked pain responses develop and potentiate progressively during the course of pain chronification.•Pain induction decreases brain volume and this effect is reversed over time.•Chronic ...pain enhances glutamate levels in the hippocampus, but not in the prefrontal cortex.•Hippocampal hyperexcitability contributes to alterations in accumbal synaptic plasticity, and to pain chronification.
Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed – an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification.
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