[18F]F-AraG

Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, ¹⁸F-labeled 2'-deoxy-2'-¹⁸F-fluoro-9-β-d-arabinofuranosylguanine ([¹⁸F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.

To test whether the myocardial [¹⁸F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [¹⁸F]F-AraG uptake in normal heart by comparing [¹⁸F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [¹⁸F]F-AraG and 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [¹⁸F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.

The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [¹⁸F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [¹⁸F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [¹⁸F]FDG signals showed wider variability at different time points. Noticeable [¹⁸F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.

Our preliminary preclinical data show that [¹⁸F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.

The objective of this study was to assess receptor expression in metastatic differentiated thyroid carcinoma patients with progressive elevated thyroglobulin and negative iodine scintigraphy, we used 68Ga-DOTATATE [Gallium-68 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)–octreotate (DOTATATE)] (Krenning’s score) and 68Ga-PSMA-11 (Gallium-68 prostate‐specific membrane antigen‐11) PET-computed tomography (CT) [molecular imaging prostate‐specific membrane antigen (miPSMA) score]. Patients with Krenning’s score 3 and above and miPSMA score 2 and above were considered to determine the incidence of patients, who would qualify for treatment with 177Lu-DOTATATE/PSMA [Lutetium-177 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)–octreotate (DOTATATE)/prostate‐specific membrane antigen]-based therapy. In addition, we compared 68Ga-DOTATATE and 68Ga-PSMA-11 PET-CT with 2-deoxy-2-[F-18]fluoroglucose (18F-FDG) PET-CT (using maximum standardized uptake value).

A total of 74 patients with histopathologically proven metastatic differentiated thyroid carcinoma with thyroglobulin elevation and negative iodine scintigraphy syndrome were studied retrospectively. They all had 18F-FDG, 68Ga-DOTATATE, and 68Ga-PSMA-11 PET-CT scans available for undertaking this analysis. The lesions detected by 68Ga-DOTATATE and 68Ga-PSMA-11 were evaluated using Krenning’s and miPSMA scores. In addition, quantitative comparisons of maximum standardized uptake values for 68Ga-DOTATATE and 68Ga-PSMA-11, as well as with 18F-FDG, were conducted.

Patient-wise analysis revealed positivity rates of 40.5% for 68Ga-DOTATATE, 41.89% for 68Ga-PSMA-11, and 75.67% for 18F-FDG. Among the 74 patients, 14 (18.91%) were deemed eligible for 177Lu-DOTATATE/PSMA-617 therapy based on Krenning’s score of 3 and above both/either miPSMA score of 2 and above on 68Ga-DOTATATE or 68Ga-PSMA-11 PET-CT. Within this subgroup, seven out of 74 patients (9.45%) were eligible for 177Lu-DOTATATE therapy, and nine out of 74 patients (12.16%) were eligible for 177Lu-PSMA-targeted therapy. Four patients were eligible for both therapies.

Among thyroglobulin elevation and negative iodine scintigraphy patient’s subgroup, 9.45% could qualify for 177Lu-DOTATATE and 12.16% for 177Lu-PSMA-617. Four were eligible for both therapies. Given the lack of effective therapies, this subset of patients warrants consideration for radionuclide therapy exploration.