Imaging

For imaging, radiodiagnostic agents are coupled with either gamma or positron emitters. Gamma cameras such as planar imaging or SPECT (single photon emission computed tomography) are used to detect gamma emitters, e.g., technetium-99m (^99mTc) or iodine-123 (¹²³I). However, positron emitters such as gallium-68 (⁶⁸Ga) and fluorine-18 (¹⁸F), which are detected using PET (positron emission tomography), provide better resolution (Yordanova A et al. 2017).

Targeted molecular imaging is used not only for the initial diagnosis of tumors but also for staging, restaging, and monitoring therapy response. The procedure is minimally invasive and utilizes only trace amounts of radiopharmaceuticals. Nonetheless, the possible benefits of the procedure should be weighed against the increase in possible health risks due to ionizing radiation exposure before every procedure (Tsai CJ et al. 2022).

Some examples of radiodiagnostic agents already in clinical use are ¹⁸F-FDG, ⁶⁸Ga-somatostatin analogs, and radiolabeled prostate-specific membrane antigen (PSMA) ligands (Weber WA et al. 2020).

SSTR-targeted Imaging

Somatostatin receptor (SSTR) targeted imaging serves not only in the initial diagnosis of patients with NETs but also in disease staging, therapeutic and surgical planning, and assessment of treatment responses (Pacak K et al. 2022).

Introducing hybrid imaging systems such as SPECT/CT and PET/CT further improved the clinical validity of SSTR-targeted imaging (del Olmo-Garcia et al. 2021). ⁶⁸Ga-DOTA-peptides detected with PET alone or combined with CT-imaging (PET/CT) were a game changer for the imaging-based diagnosis, staging, and follow-up of patients with NETs (Eychenne R et al. 2020). The advantages of ⁶⁸Ga-labeled SSTR ligands include improved image resolution, higher sensitivity and specificity, and decreased imaging time and radiation doses compared to scintigraphy and conventional imaging. A high-quality ⁶⁸Ga PET/CT requires a moderate dose of 100-200 MBq (Virgolini et al. 2010). In addition to its excellent physical properties, gallium-68 is available from a commercial clinical-grade generator, an essential advantage for clinical applications.

References:

• Yordanova, Anna et al. 2017. “Theranostics in Nuclear Medicine Practice.” OncoTargets and therapy 10: 4821–28. DOI: 10.2147/OTT.S140671

• Tsai, Chi-Jung et al. 2022. “Very-Low-Dose Radiation and Clinical Molecular Nuclear Medicine.” Life 12(6): 912. DOI: 10.3390/life12060912

• Weber, Wolfgang A. et al. 2020. “The Future of Nuclear Medicine, Molecular Imaging, and Theranostics.” Journal of Nuclear Medicine 61(Supplement 2): 263S-272S. DOI: 10.2967/jnumed.120.254532

• Turner 2018. “Recent Advances in Theranostics and Challenges for the Future.” The British Journal of Radiology 91(1091): 20170893. DOI: 10.1259/bjr.20170893

• Pacak, Karel et al. 2022. “Functional Imaging of Neuroendocrine Tumors: Stacking the Odds in a Patient’s Favor.” The Journal of Clinical Endocrinology & Metabolism, 107(9), e3953–e3954. DOI: 10.1210/clinem/dgac298

• del Olmo-Garcia, Maria I. et al. 2021. “Somatostatin and Somatostatin Receptors: From Signaling to Clinical Applications in Neuroendocrine Neoplasms.” Biomedicines, 9(12), Article 12. DOI: 10.3390/biomedicines9121810

• Eychenne, Romain et al. 2020. “Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy.” Molecules, 25(17), Article 17. DOI: 10.3390/molecules25174012

• Virgolini, Irene et al. 2010. “Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE.” European Journal of Nuclear Medicine and Molecular Imaging, 37(10), Article 10. DOI: 10.1007/s00259-010-1512-3