•Enlarged lateral ventricles heavily affect the spatial normalization performance.•Suitable CT-guided normalization for brains with enlarged lateral ventricles.•CT-guided normalization of SPECT is a ...reliable method for quantitative studies.•Less biased SPECT quantification in caudate thanks to normalization improvement.
Spatial normalization is a prerequisite step for the quantitative analysis of SPECT or PET brain images using volume-of-interest (VOI) template or voxel-based analysis. MRI-guided spatial normalization is the gold standard, but the wide use of PET/CT or SPECT/CT in routine clinical practice makes CT-guided spatial normalization a necessary alternative. Ventricular enlargement is observed with aging, and it hampers the spatial normalization of the lateral ventricles and striatal regions, limiting their analysis. The aim of the present study was to propose a robust spatial normalization method based on CT scans that takes into account features of the aging brain to reduce bias in the CT-guided striatal analysis of SPECT images.
We propose an enhanced CT-guided spatial normalization pipeline based on SPM12. Performance of the proposed pipeline was assessed on visually normal 123I-FP-CIT SPECT/CT images. SPM12 default CT-guided spatial normalization was used as reference method. The metrics assessed were the overlap between the spatially normalized lateral ventricles and caudate/putamen VOIs, and the computation of caudate and putamen specific binding ratios (SBR).
In total 231 subjects (mean age ± SD = 61.9 ± 15.5 years) were included in the statistical analysis. The mean overlap between the spatially normalized lateral ventricles of subjects and the caudate VOI and the mean SBR of caudate were respectively 38.40 % (± SD = 19.48 %) of the VOI and 1.77 (± 0.79) when performing SPM12 default spatial normalization. The mean overlap decreased to 9.13 % (± SD = 1.41 %, P < 0.001) of the VOI and the SBR of caudate increased to 2.38 (± 0.51, P < 0.0001) when performing the proposed pipeline. Spatially normalized lateral ventricles did not overlap with putamen VOI using either method. The mean putamen SBR value derived from the proposed spatial normalization (2.75 ± 0.54) was not significantly different from that derived from the default SPM12 spatial normalization (2.83 ± 0.52, P > 0.05).
The automatic CT-guided spatial normalization used herein led to a less biased spatial normalization of SPECT images, hence an improved semi-quantitative analysis. The proposed pipeline could be implemented in clinical routine to perform a more robust SBR computation using hybrid imaging.
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Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency ...of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions. However scintigraphy appears better suited for a biodistribution study owing to a great sensitivity. The successful immobilization of radioelements ((99m)Tc, (111)In) in the DTDTPA shell, instead of gadolinium ions, renders possible the follow up of Au@DTDTPA by scintigraphy which showed that Au@DTDTPA nanoparticles exhibit a safe behaviour after intravenous injection to healthy rats.
Ultrasmall gadolinium-based nanoparticles (GBNs) induce both a positive contrast for magnetic resonance imaging and a radiosentizing effect. The exploitation of these characteristics leads to a ...greater increase in lifespan of rats bearing brain tumors since the radiosensitizing effect of GBNs can be activated by X-ray microbeams when the gadolinium content is, at the same time, sufficiently high in the tumor and low in the surrounding healthy tissue. GBNs exhibit therefore an interesting potential for image-guided radiotherapy.
Functionalized gold nanoparticles were applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. These particles were obtained by encapsulating gold cores within a ...multilayered organic shell which is composed of gadolinium chelates bound to each other through disulfide bonds. The contrast enhancement in MRI stems from the presence of gadolinium ions which are entrapped in the organic shell, whereas the gold core provides a strong X-ray absorption. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in the lungs, spleen, and liver.
Background
To show the equivalence between the specific binding ratios (SBR) of visually normal
123
I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without ...dopaminergic degeneration to allow their use as a reference database.
Methods
The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB:
n
= 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB:
n
= 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB:
n
= 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT.
Results
The dispersion parameters,
R
2
and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: − 4.94% for ScanOnlyDB, − 4.65% for NoDG5YearsDB, − 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (
P
< 10
–5
) and NoDG5YearsDB (
P
< 10
–2
). The age-gender interaction was significant only for ScanOnlyDB (
P
< 10
–2
), and the p-value decreased to 10
–6
after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction.
Conclusion
SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis.
The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which ...constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor.
Nanometric hybrid gadolinium oxide particles (Gado-6Si-NP) for diagnostic and therapeutic applications (mean diameter 3–4 nm) were obtained by encapsulating Gd2O3 cores within a polysiloxane shell, ...which carries organic fluorophore (Cy 5) and is derivatized by a hydrophilic carboxylic layer. As residency time in the living body and methods of waste elimination are crucial to defining a good nanoparticle candidate and moving forward with steps for validation, this study was aimed at evaluating the biodistribution of these multimodal Gado-6Si-NP in rodents. Gado-6Si-NP were imaged following intravenous injection in control Wistar rats and mice using MRI (7 T), optical fluorescent imaging, and SPECT. A clear correlation was observed among MRI, optical imaging, and SPECT regarding the renal elimination. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles circulated freely in the blood pool and were rapidly cleared by renal excretion without accumulation in liver and RES uptake. These results demonstrate that Gado-6Si-NP display optimal biodistribution properties, enabling them to be developed as multimodal agents for in vivo imaging and theragnostics, especially in oncological applications.
Introduction
Despite growing evidence of a superior diagnostic performance of
68
Ga-PSMA-11 over
18
F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is ...still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11.
Patients and methods
Six centres performed
68
Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient’s data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed.
Results
(1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1–3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients’ age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide.
Conclusion
Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (
n
> 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases.
Abstract Gadolinium based nanoparticles (GBNs, diameter 2.9 ± 0.2 nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of ...these GBNs in experimental radioresistant human head and neck squamous cell carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6 mM GBNs with 250 kV photon irradiation significantly decreased SQ20B cell survival, associated with an increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, and the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10 Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors. From the Clinical Editor Gadolinium-based nanoparticles are studied as radiosensitizing theranostic agents to address head and neck squamous cell carcinoma in this novel study, demonstrating a promising adjuvant to radiotherapy for these often treatment resistant tumors.
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