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One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for ^99mTc radiolabelling of peptides.

ABSTRACT: Radiotracers labelled with technetium-99m (^99mTc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst ^99mTc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no ^99mTc-labelled receptor-targeted radiopharmaceuticals in widespread clinical use. This is in part due to the multistep radiosyntheses required for the latter. We demonstrate that the diphosphine, 2,3-bis(diphenylphosphino)maleic anhydride (BMA), is an excellent platform for preparation of kit-based, receptor-targeted ^99mTc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with ^99mTc using one-step, kit-based protocols. Here, reaction of BMA with the α_vβ₃-integrin receptor targeted cyclic peptide, Arg-Gly-Asp-DPhe-Lys (RGD), provided the first diphosphine-peptide conjugate, DP-RGD. DP-RGD was incorporated into a "kit", and addition of a saline solution containing ^99mTcO₄^- to this kit, followed by heating, furnished the radiotracer [^99mTcO₂(DP-RGD)₂]⁺ in consistently high radiochemical yields (>90%). The analogous [ReO₂(DP-RGD)₂]⁺ compound was prepared and characterised, revealing that both [^99mTcO₂(DP-RGD)₂]⁺ and [ReO₂(DP-RGD)₂]⁺ consist of a mixture of cis and trans geometric isomers. Finally, [^99mTcO₂(DP-RGD)₂]⁺ exhibited high metabolic stability, and selectively targeted α_vβ₃-integrin receptors, enabling in vivo SPECT imaging of α_vβ₃-integrin receptor expression in mice.

SUBMITTER: Hungnes IN

PROVIDER: S-EPMC8594432 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:PurposeInvestigate the impact of acquisition time and reconstruction parameters on single-photon emission computed tomography/computed tomography (SPECT/CT) image quality with the ultimate aim of finding the shortest possible acquisition time for clinical whole-body SPECT/CT (WB-SPECT/CT) while maintaining image quality METHODS: The National Electrical Manufacturers Association (NEMA) image quality measurements were performed on a SPECT/CT imaging system using a NEMA International Electrotechnical Commission (IEC) phantom with spherical inserts of varying diameter (10-37 mm), filled with 99m Tc in activity sphere-to-background concentration ratio of 8.5:1. A gated acquisition was acquired and binned data were summed to simulate acquisitions of 15, 8, and 3 s per projection angle. Images were reconstructed on a Hermes (HERMES Medical Solutions AB, Stockholm, Sweden) workstation using eight subsets and between 4 and 24 iterations of the three-dimensional (3D) ordered subset expectation maximization (OSEM) algorithm. Reconstructed images were post-smoothed with 3D Gaussian filter ranging from 0 to 12 mm full-width at half maximum (FWHM). Contrast recovery, background variability, and contrast-to-noise ratio were evaluated RESULTS: As expected, the spheres were more clearly defined as acquisition time and count statistics improved. The optimal iteration number and Gaussian filter were determined from the contrast recovery convergence and level of noise. Convergence of contrast recovery was observed at eight iterations while 12 iterations yielded stabilized values at all acquisition times. In addition, it was observed that applying 3D Gaussian filter of 8-12 mm FWHM suppressed the noise and mitigated Gibbs artifacts. Background variability was larger for small spheres than larger spheres and the noise decreased when acquisition time became longer. A contrast-to-noise ratio >5 was reached for the two smallest spheres of 10 and 13 mm at acquisition times of 8 s CONCLUSION: Optimized reconstruction parameters preserved image quality with reduce acquisition time in present study. This study suggests an optimal protocol for clinical 99m Tc SPECT/CT can be reached at 8 s per projection angle, with data reconstructed using 12 iterations and eight subset of the 3D OSEM algorithm and 8 mm Gaussian post-filter.

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One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for ^99mTc radiolabelling of peptides.

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Dataset Information

One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for 99mTc radiolabelling of peptides.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for ^99mTc radiolabelling of peptides.