Our goal was to validate the feasibility of 99mTc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of 99mTc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline. 99mTc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy. 99mTc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of 99mTc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of 99mTc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.

BACKGROUND AND PURPOSE: To detect brain morphological alterations in patients with early Parkinson's disease (PD) by using magnetic resonance imaging (MRI) morphometry under radiological diagnostic conditions. METHODS: T1-weighted brain images of 18 early PD patients and 18 age-sex-matched healthy controls (HCs) were analyzed with free software Computational Anatomy Toolbox (CAT12). Regional cortical thickness (rCTh) in 68 atlas-defined regionsof-interest (ROIs) and subcortical gray matter volume (SGMV) in 14 atlas-defined ROIs were determined and compared between patients and HCs by paired comparison using both ROI-wise and voxel-wise analyses. False-discovery rate (FDR) was used multiple comparison correction. Possible correlations between brain morphological changes in patients and clinical observations were also analyzed. RESULTS: Comparing to the HCs, the ROI-wise analysis revealed rCTh thinning significantly in left medial orbitofrontal (P = .001), by trend (P < .05 but not significant after FDR correction) in four other ROIs located in frontal and temporal lobes, and a volume decreasing trend in left pallidum of the PD patients, while the voxel-wise analysis revealed one cluster with rCTh thinning trend located between left insula and superior temporal region of the patients. In addition, the patients showed more distinct rCTh thinning in ipsilateral hemisphere and SGMV deceasing trends in contralateral hemisphere in respect of the symptom-onset body side. CONCLUSION: Brain morphological alterations in early PD patients are evident despite of their inconspicuous findings in standard MRI. Quantitative morphological measurements with CAT12 may be an applicable add-on tool for clinical diagnosis of early PD. These results have to be verified in future studies with larger patient samples.

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BackgroundBlood vessels in tumors express higher level of aminopeptidase N (APN) than normal tissues. Evidence suggests that the CNGRC motif is an APN ligand which targets tumor vasculature. Increased expression of APN in tumor vascular endothelium, therefore, offers an opportunity for targeted delivery of NGR peptide-linked drugs to tumors.Methods/Principal FindingsTo determine whether an additional cyclic CNGRC sequence could improve endothelial cell homing and antitumor effect, human plasminogen kringle 5 (hPK5) was modified genetically to introduce a CNGRC motif (NGR-hPK5) and was subsequently expressed in yeast. The biological activity of NGR-hPK5 was assessed and compared with that of wild-type hPK5, in vitro and in vivo. NGR-hPK5 showed more potent antiangiogenic activity than wild-type hPK5: the former had a stronger inhibitory effect on proliferation, migration and cord formation of vascular endothelial cells, and produced a stronger antiangiogenic response in the CAM assay. To evaluate the tumor-targeting ability, both wild-type hPK5 and NGR-hPK5 were 99 mTc-labeled, for tracking biodistribution in the in vivo tumor model. By planar imaging and biodistribution analyses of major organs, NGR-hPK5 was found localized to tumor tissues at a higher level than wild-type hPK5 (approximately 3-fold). Finally, the effects of wild-type hPK5 and NGR-modified hPK5 on tumor growth were investigated in two tumor model systems. NGR modification improved tumor localization and, as a consequence, effectively inhibited the growth of mouse Lewis lung carcinoma (LLC) and human colorectal adenocarcinoma (Colo 205) cells in tumor-bearing mice.Conclusions/SignificanceThese studies indicated that the addition of an APN targeting peptide NGR sequence could improve the ability of hPK5 to inhibit angiogenesis and tumor growth.

Recent successes in monitoring and diagnosing a variety of tumors using 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) imaging encouraged us to expand the use of this tracer. This case-control study aimed to evaluate the feasibility of 99mTc-3PRGD2 imaging for detecting choroidal melanoma (CM) and for monitoring tumor response to plaque brachytherapy (PB). Ten consecutive patients with CM who underwent 99mTc-3PRGD2 imaging before and 3 months after PB were reviewed. The tumor-to-occipital bone (T/O) and mirrored contralateral normal tissue-to-occipital bone (N/O) ratios were calculated by region of interest analysis at baseline and 3 months post-PB. T/O values were compared between patients with CM with comorbid secondary retinal detachment (RD) and those without RD. The relationship between T/O value and tumor volume was also investigated. 99mTc-3PRGD2 SPECT/CT showed focal uptake in CM. The mean T/O ratio before PB was 1.90 ± 1.26 and the mean N/O ratio was 0.80 ± 0.21 (P = .02). The 99mTc-3PRGD2 concentrations in 5 patients with CM with RD were higher (T/O = 2.69 ± 1.39) than in those without secondary RD (T/O = 1.10 ± 0.18) (P = .008). T/O ratios at 3 months post-PB were significantly lower than that at baseline (1.23 ± 0.59, P = .03). There was a linear relationship between T/O and tumor volume (y-hat = 0.028 + 0.003x, R2 = 0.768, P = .001). The 95% confidence interval for the (T/O)/volume ratio was 0.002 to 0.005. 99mTc-3PRGD2 imaging is a feasible modality for the diagnosis of CM. Furthermore, follow-up for at least 20 months after PB indicated that coanalysis of 99mTc-3PRGD2 imaging and tumor volume may provide a promising prognostic predictor in patients with CM.