Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Abstract

Radioembolization with 90 Y microspheres represents a novel transarterial radiation treatment for liver tumors. The purpose of this pilot study was to evaluate the findings of postimplantation PET/CT of 90 Y glass microspheres. Methods: Three patients with hepatocellular carcinoma and 2 patients with liver metastases (1 neuroendocrine, 1 colorectal) underwent PET/CT after radioembolization. Four patients underwent imaging at 1 mo to assess response and confirm PET/CT findings; 1 patient underwent PET/CT at 4 d after 90 The tracer 90 Y is traditionally thought of as a pure b-emitter. Thus, current clinical practice involves determining the distribution of the microspheres through bremsstrahlung imaging combined with anatomic imaging via SPECT/CT (1). Because bremsstrahlung imaging is based on a SPECT acquisition that uses either a wide imaging window or multiple energy windows due to the continuum, the scattered photon cannot easily be distinguished from true photons. Consequently, bremsstrahlung imaging is not quantifiable, and thus accurate dose distribution cannot be obtained (2).In an effort to improve pretreatment evaluation and follow-up, microspheres containing radionuclides that emit both b-and g-radiations have been proposed, and treatment with microspheres includes the use of 166 Ho and 186 Re/ 188 Re. At the time of this article's publication, glass and poly (L-lactic acid) (PLLA) microspheres incorporating 186 Re/ 188 Re had not been tested in human subjects with liver tumors. However, 188 Re human serum albumin microspheres ( 188 Re-HSAM) have been tested in a small cohort of patients at a single institution (3). The maximum b-particle energy of 188 Re (2.12 MeV) is lower than that of 90 Y (2.28 MeV), thus necessitating 4-to 5-fold-higher activities to obtain an absorbed dose equivalent to that of 90 Y. Because the g-energy (155 keV) is comparable to other nuclear medicine imaging agents, 188 Re-HSAM seems to be a good candidate for radioembolization of liver tumors. However, no conclusive effects could be derived from the study performed by Liepe et al. because of the small cohort size and heterogeneity of the patients' primary disease (3). To properly evaluate the effect of radioembolization of hepatic malignancies with 188 Re-HSAM, more studies and a larger patient cohort are warranted.Another promising radionuclide proposed for radioembolization of hepatic tumors is 166 Ho (maximum energy of the b-particle, 1.77 [48.7%] and 1.85 [50.5%] MeV and energy of the g-ray, 81 keV [6.7%]). 166 Ho PLLA microspheres are currently being used in patients with hepatic malignancies under a phase I clinical trial (4,5). Similar to the 188 Re HSAM dosimetry, the absorbed radiation dose per activity of 166 Ho (8.7 mGy/MBq) is lower than that of 90 Y (28 mGy/MBq). As a result, with 166 Ho 3 times the radioactivity will be required for radioembolization to achieve a dosimetry equivalent to that of 90 Y. The greatest advantage of 166 Ho is that it represents a multimodality imaging agent (6). The paramagnetic pro...

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…Adequate visualisation can be achieved with a 20 minute per bed scan [117,118] and sensitivities of 0.11 cps/MBq in patients [119], 0.577 and 1 cps/MBq in phantom [117,120] have been reported. In a recent study, the optimal contrast for hot and cold spheres in a phantom was obtained with LYSO crystals and TOF technology [121].…”

Semi-Quantitative Analysis of Post-Transarterial Radioembolization 90Y Microsphere Positron Emission Tomography Combined with Computed Tomography (PET/CT) Images in Advanced Liver Malignancy: Comparison With 99mTc Macroaggregated Albumin (MAA) Single Photon Emission Computed Tomography (SPECT)

“…Within 24 h after microsphere administration, the patients were scanned using a PET/CT scanner (Gemini TF PET/CT, Philips Healthcare) with a conventional 18 F energy window (511 keV) and timeof-flight (TOF) mode including attenuation correction. According to the liver size of the patient, one or two imaging bed positions were selected.…”

“…Recent studies report the feasibility of high-resolution 90 Y positron emission tomography/computed tomography (PET/ CT) imaging using time-of-flight (TOF) technology and the possibility of the posttreatment evaluation of 90 Y microsphere distribution with 90 Y PET/CT [17][18][19].…”

The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: a systematic review

“…Post-treatment imaging with PET, based on the internal pair production of 90 Y once every 32 million decays, has substantially improved the posttreatment quantification of 90 Y-microspheres. [48,49,50] Furthermore, our institute has developed holmium-166 ( 166 Ho) poly (Llactic acid) microspheres to allow for quantitative imaging of microsphere distribution. [51,52] In addition to high-energy beta radiation, 166 Ho also emits gamma-radiation and thereby facilitates imaging by gamma scintigraphy and SPECT.…”