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Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-^99mTc-Tricarbonyl Complex.

ABSTRACT: The in vivo biodistribution of liposomal formulations greatly influences the pharmacokinetics of these novel drugs; therefore the radioisotope labeling of liposomes and the use of nuclear imaging methods for in vivo studies are of great interest. In the present work, a new procedure for the surface labeling of liposomes is presented using the novel ^99mTc-tricarbonyl complex. Liposomes mimicking the composition of two FDA approved liposomal drugs were used. In the first step of the labeling, thiol-groups were formed on the surface of the liposomes using Traut's reagent, which were subsequently used to bind ^99mTc-tricarbonyl complex to the liposomal surface. The labeling efficiency determined by size exclusion chromatography was 95%, and the stability of the labeled liposomes in bovine serum was found to be 94% over 2 hours. The obtained specific activity was 50?MBq per 1??mol lipid which falls among the highest values reported for ^99mTc labeling of liposomes. Quantitative in vivo SPECT/CT biodistribution studies revealed distinct differences between the labeled liposomes and the free ^99mTc-tricarbonyl, which indicates the in vivo stability of the labeling. As the studied liposomes were non-PEGylated, fast clearance from the blood vessels and high uptake in the liver and spleen were observed.

SUBMITTER: Varga Z

PROVIDER: S-EPMC5612672 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-<sup>99m</sup>Tc-Tricarbonyl Complex.

Varga Zoltán Z Szigyártó Imola Cs IC Gyurkó István I Dóczi Rita R Horváth Ildikó I Máthé Domokos D Szigeti Krisztián K

Contrast media & molecular imaging 20170531

The in vivo biodistribution of liposomal formulations greatly influences the pharmacokinetics of these novel drugs; therefore the radioisotope labeling of liposomes and the use of nuclear imaging methods for in vivo studies are of great interest. In the present work, a new procedure for the surface labeling of liposomes is presented using the novel <sup>99m</sup>Tc-tricarbonyl complex. Liposomes mimicking the composition of two FDA approved liposomal drugs were used. In the first step of the lab ...[more]

PMID: 29097923

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Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:BackgroundQuantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions.MethodsA retrospective study was carried out involving 221 patients (116 males and 105 females) who underwent SPECT/CT scan using 99mTc-MDP. The maximum SUV (SUVmax), mean SUV (SUVmean) and CT values (Hounsfield Unit, HU) of 2416 normal vertebrae bodies, 157 benign bone lesions and 118 malignant bone metastasis foci were obtained. The correlations between SUVmax of normal vertebrae and CT values of normal vertebrae, age, height, weight, BMI of patients were analyzed. Statistical analysis was performed with data of normal, benign and malignant groups corresponding to same sites and gender.ResultsThe SUVmax and SUVmean of normal vertebrae in males were markedly higher than those in females (P < 0.0009). The SUVmax of each normal vertebral segment showed a strong negative correlation with CT values in both males and females (r = - 0.89 and - 0.92, respectively; P < 0.0009). The SUVmax of normal vertebrae also showed significant correlation with weight, height, and BMI in males (r = 0.4, P < 0.0009; r = 0.28, P = 0.005; r = 0.22, P = 0.026), and significant correlation with weight and BMI in females (r = 0.32, P = 0.009; r = 0.23, P = 0.031). The SUVmax of normal group, benign bone lesion group and malignant bone metastasis foci group showed statistical differences in both males and females.ConclusionOur study evaluated SUVmax and SUVmean of normal vertebrae, benign bone lesion and malignant bone metastasis foci with a large sample population. Preliminary results proved the potential value of SUVmax in differentiation benign and malignant bone lesions. The results may provide a quantitative reference for clinical diagnosis and the evaluation of therapeutic response in vertebral lesions.

Project description:PurposeAccurate dosimetry is essential in radioembolization. To this purpose, an automatic protocol for healthy liver dosimetry based on dual isotope (DI) SPECT imaging, combining holmium-166 (166Ho)-microspheres, and technetium-99?m (99mTc)-colloid was developed: 166Ho-microspheres used as scout and therapeutic particles, and 99mTc-colloid to identify the healthy liver. DI SPECT allows for an automatic and accurate estimation of absorbed doses, introducing true personalized dosimetry. However, photon crosstalk between isotopes can compromise image quality. This study investigates the effect of 99mTc downscatter on 166Ho dosimetry, by comparing 166Ho-SPECT reconstructions of patient scans acquired before (166Ho-only) and after additional administration of 99mTc-colloid (166Ho-DI).MethodsThe 166Ho-only and 166Ho-DI scans were performed in short succession by injecting 99mTc-colloid on the scanner table. To compensate for 99mTc downscatter, its influence was accounted for in the DI image reconstruction using energy window-based scatter correction methods. The qualitative assessment was performed by independent blinded comparison by two nuclear medicine physicians assessing 65 pairs of SPECT/CT. Inter-observer agreement was tested by Cohen's kappa coefficient. For the quantitative analysis, two volumes of interest within the liver, VOITUMOR, and VOIHEALTHY were manually delineated on the 166Ho-only reconstruction and transferred to the co-registered 166Ho-DI reconstruction. Absorbed dose within the resulting VOIs, and in the lungs (VOILUNGS), was calculated based on the administered therapeutic activity.ResultsThe qualitative assessment showed no distinct clinical preference for either 166Ho-only or 166Ho-DI SPECT (kappa = 0.093). Quantitative analysis indicated that the mean absorbed dose difference between 166Ho-DI and 166Ho-only was - 2.00 ± 2.84?Gy (median 27?Gy; p value < 0.00001), - 5.27 ± 8.99?Gy (median 116?Gy; p value = 0.00035), and 0.80 ± 1.08?Gy (median 3?Gy; p value < 0.00001) for VOIHEALTHY, VOITUMOR, and VOILUNGS, respectively. The corresponding Pearson's correlation coefficient between 166Ho-only and 166Ho-DI for absorbed dose was 0.97, 0.99, and 0.82, respectively.ConclusionThe DI protocol enables automatic dosimetry with undiminished image quality and accuracy.Clinical trialsThe clinical study mentioned is registered with Clinicaltrials.gov (NCT02067988) on 20 February 2014.

Project description:PurposeCheckpoint inhibition therapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is now standard management of non-small cell lung cancer (NSCLC). PD-L1 expression is a validated and approved prognostic and predictive biomarker for anti-PD-1/PD-L1 therapy. Technetium-99 m [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in NSCLC, presenting an opportunity for non-invasive assessment. The aim of this study was to determine the inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC.Methods[99mTc]NM-01 SPECT/CT studies of 21 consecutive NSCLC participants imaged for the evaluation of PD-L1 expression were analysed. Three independent observers measured maximum counts in a tumour region of interest (ROImax) of primary lung, metastatic lesions and normal tissue references of both 1 and 2 h post-injection (n = 42) anonymised studies using a manual technique. Intraclass correlation coefficients (ICC) were calculated, and Bland-Altman plot analysis was performed to determine inter- and intraobserver agreement.ResultsIntraclass correlation of primary lung tumour-to-blood pool (T:BP; ICC 0.83, 95% CI 0.73-0.90) and lymph node metastasis-to-blood pool (LN:BP; ICC 0.87, 0.81-0.92) measures of [99mTc]NM-01 uptake was good to excellent between observers. Freehand ROImax of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues also demonstrated excellent interobserver agreement. ROImax scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch (ICC 0.89). Manual ROImax re-scoring of T, LN, T:BP and LN:BP using [99mTc]NM-01 SPECT/CT following a 42-day interval was consistent with excellent intraobserver agreement (ICC range 0.95-0.97).ConclusionGood to excellent inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC was demonstrated in this study, including T:BP which has been shown to correlate with PD-L1 status. [99mTc]NM-01 SPECT/CT has the potential to reliably and non-invasively assess PD-L1 expression.Clinical trial registrationClinicalTrials.gov identifier no. NCT02978196. Registered 30th November 2016.

Dataset Information

Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-99mTc-Tricarbonyl Complex.

Publications

Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-<sup>99m</sup>Tc-Tricarbonyl Complex.

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Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-^99mTc-Tricarbonyl Complex.