Biodistribution and radiodosimetry of a novel myocardial perfusion tracer 123I-CMICE-013 in healthy rats

Duan, Yin; Lockwood, Julia; Wei, Lihui; Hunter, Chad; Soueidan, Karen; Bensimon, Corinne; Fernando, Pasan; Wells, R. Glenn; Ruddy, Terrence D.

doi:10.1186/2191-219x-4-16

Cited by 6 publications

(2 citation statements)

References 25 publications

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“…Statistical analysis of the correlation between data acquired by in vivo SPECT and ex vivo biodistribution was evaluated with linear regression analysis and a Pearson correlation coefficient (r) using the SciPy package in Python (Finucane et al 2011, Duan et al 2014, Virtanen et al 2020. Statistical significance was set as p < 0.05.…”

Section: Discussionmentioning

confidence: 99%

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

Koniar,

Wharton,

Ingham

et al. 2024

Phys. Med. Biol.

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Objective. 225Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy (TAT), however, 225Ac (t1/2 = 9.9 d) lacks direct gamma emissions for in vivo imaging. 226Ac (t1/2 = 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of 225Ac radiopharmaceuticals. 226Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study for in vivo quantitative 226Ac SPECT imaging and validation of activity estimation. Approach. 226Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [226Ac]Ac3+ was radiolabelled with the bioconjugate crown-TATE developed for therapeutic targeting of neuroendocrine tumours (NET). Mice with AR42J tumour xenografts were injected with either 2 MBq of [226Ac]Ac-crown-TATE or 4 MBq of free [226Ac]Ac3+ activity and were scanned at 1, 2.5, 5, and 24 h post injection in a preclinical microSPECT/CT. Quantitative SPECT images were reconstructed from the 158 keV and 230 keV photopeaks with attenuation, background, and scatter corrections. Image-based 226Ac activity measurements were assessed from volumes of interest (VOIs) within tumours and organs of interest. Imaging data was compared with ex vivo biodistribution measured via gamma counter. Main Results. We present, to the best of our knowledge, the first ever in vivo quantitative SPECT images of 226Ac activity distributions. Time-activity curves derived from SPECT images quantify the in vivo biodistribution of [226Ac]Ac-crown-TATE and free [226Ac]Ac3+ activity. Image-based activity measurements in the tumours and organs of interest corresponded well with ex vivo biodistribution measurements. Significance. Here in, we established the feasibility of in vivo 226Ac quantitative SPECT imaging for accurate measurement of actinium biodistribution in a preclinical model. This imaging method could quantitative in vivo pharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency.

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Section: Discussionmentioning

confidence: 99%

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

Koniar,

Wharton,

Ingham

et al. 2024

Phys. Med. Biol.

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“…CMICE-013 has a good toxicity profile (8), and initial biodistribution studies in rats demonstrated excellent uptake in the heart and contrast with surrounding organs. The effective dose of a 185-MBq injection was estimated from preclinical studies to be 1.3-3.9 mSv (9,10). This study's objectives were to assess the image quality of CMICE-013 and compare its uptake with tetrofosmin, sestamibi, and 201 Tl in vivo in a porcine model of myocardial ischemia.…”

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confidence: 99%

Flow-Dependent Uptake of ¹²³I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers

et al. 2015

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Rotenone derivatives have shown promise in myocardial perfusion imaging (MPI). CMICE-013 is a novel 123 I-labeled rotenone derivative developed for SPECT MPI. The objective of this study was to assess the image quality of CMICE-013 and compare its uptake with tetrofosmin, sestamibi, and 201 Tl in vivo in a porcine model of stress-induced myocardial ischemia. Methods: Microspheres were injected simultaneously with the radiotracer injections at rest and stress to measure blood flow. Mimicking a 1-d tetrofosmin protocol, stress imaging used 3 times as much activity and occurred 1 h after the rest injection. SPECT images were obtained at both rest and stress. After imaging, the heart was sectioned into 44-50 pieces. In each heart sample, the tracer uptake was measured in a γ counter. The images were aligned, and the decay-corrected ratio of the signals at rest and stress was used to separate the well-counter signal into rest and stress components. The uptake at rest and stress was compared with microsphere flow measurements. Results: The CMICE-013 images showed good contrast between the heart and surrounding organs, with heart-to-liver and heart-to-lung uptake ratios similar to those of the standard tracers. Uptake of CMICE-013 was 1.5% of the injected dose at rest and increased more rapidly with increased blood flow than did the standard SPECT tracers. The percentage injected dose of CMICE-013 taken up by the heart was greater (P , 0.05) than 201 Tl, tetrofosmin, or sestamibi at flows greater than 1.5 mL/min/g. Conclusion: CMICE-013 is a promising new SPECT MPI agent. Repeat ed unexpected shutdowns of several of the major nuclear reactors producing 99 Mo has led to ongoing concern over the stability of the supply of 99m Tc and, consequently, interest in developing alternative tracers. Myocardial perfusion imaging (MPI) remains one of the more common tests performed with 99m Tclabeled agents. For MPI, PET is a potential option using either 82 Rb or 13 N ammonia, because the parent isotope for 82 Rb generators ( 82 Sr) and ammonia are both cyclotron-produced. Interest in PET MPI is growing; however, the number of MPI SPECT scans obtained annually in North America is still orders of magnitude larger and likely to remain so for many years. Thus, a SPECT alternative to 99m Tc MPI tracers remains an important goal.Clinical trials of the 18 F-labeled PET tracer flurpiridaz (1,2) have shown excellent contrast between the heart and surrounding organs and performance superior to standard 99m Tc-based tracers for the identification of disease. This tracer inhibits mitochondrial complex I and derives its specificity for cardiac imaging from the high concentration of mitochondria in the heart. Other compounds that target mitochondrial complex I have been studied previously in SPECT. An iodinated rotenone compound (I-ZIROT) was shown to have excellent uptake in the heart and excellent extraction at higher blood flows (3,4), which is in contrast to the standard SPECT 99m Tc tracers that have a roll-off in their extraction, prod...

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Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging

Hunter

Hill

Ziadi

et al. 2015

Eur J Nucl Med Mol Imaging

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Biodistribution and radiodosimetry of a novel myocardial perfusion tracer 123I-CMICE-013 in healthy rats

Cited by 6 publications

References 25 publications

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

Flow-Dependent Uptake of ¹²³I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers

Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging

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Biodistribution and radiodosimetry of a novel myocardial perfusion tracer 123I-CMICE-013 in healthy rats

Cited by 6 publications

References 25 publications

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

Flow-Dependent Uptake of 123I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers

Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging

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Flow-Dependent Uptake of ¹²³I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers