Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres

Abstract

Background: Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry.

Methods: Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET.

Results: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%).

Conclusions: Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

Figure 1

Example of a ⁹⁰Y PET/CT phantom scan with maximum intensity projection image. (a) Trans-axial, (b) coronal, and (c) sagittal planes. This scan shows our lowest tested vial sediment activity of 3.5 MBq (≈3 MBq/ml). The upper PET visual display threshold of this scan was adjusted to 114% (2,000 kBq/ml) to minimize visual interference from background noise [1]. (d) Maximum intensity projection image of the same phantom scan (arrow indicates vial sediment) with the upper PET visual display threshold adjusted to 1% (20 kBq/ml) to reveal the underlying background noise as an example to readers [1].

Figure 2

Detector linearity. Linear regression line (dotted) of total vial sediment activities quantified by ⁹⁰Y PET versus that of a dose calibrator.

Figure 3

Patient 9. ⁹⁰Y radioembolization of an organ other than the liver. KIT-negative GIST with bulky metastasis to the right adrenal gland, refractory to tyrosine kinase inhibitors. Angiography was previously shown in part 1 [1]. (a) Catheter-directed CT angiogram of the right inferior adrenal artery delineates the targeted right adrenal tumor measuring 10.1 × 6.3 cm. (b) Post-radioembolization ⁹⁰Y PET/CT depicts microsphere biodistribution in high resolution, with concordant activity within targeted regions of contrast-enhancing tumor. Low-grade activity seen in the adjacent right liver lobe is due to ⁹⁰Y radioembolization of a segment IV metastasis. (c) Isodose map by voxel dosimetry of the corresponding trans-axial slice of the right adrenal tumor provides a visual representation of dose heterogeneity within the tumor and adjacent right liver lobe and displays the full dose range from 0 to >1,000 Gy. (d) Follow-up contrast-enhanced CT of the abdomen at 9.5 months shows a moderate size reduction to 7.6 × 4.6 cm, representing a partial response.

Figure 4

⁹⁰Y DVH of the right adrenal gland GIST metastasis generated by ⁹⁰Y PET voxel dosimetry. Continued from Figure 3. A partial response was achieved at D₇₀ 53 Gy.

Figure 5

⁹⁰Y DVH of seven HCC tumors, ranging in size from 25.0 to 3,341.1 cm³.

Figure 6

Patient 10. (a) Catheter-directed CT angiogram of the anterior branch of the right hepatic artery, supplying segments V and VIII, demonstrates contrast enhancement of a large portal vein tumor thrombus (arrow). (b, c) A ⁹⁰Y PET VOI of the activity within the portal vein tumor thrombus was defined by volumetric isocontour thresholding, visually constrained to its anatomical margins as seen on the catheter-directed CT angiography. Within this VOI, the mean ⁹⁰Y radioconcentration at the time of scan (5,239.8 kBq/ml) was decay-corrected back to the time of ⁹⁰Y radioembolization (6,653 kBq/ml). By ⁹⁰Y MIRD macrodosimetry, the mean absorbed dose of the portal vein tumor thrombus was approximately 316 Gy within the VOI. (d) Follow-up triphasic CT of the liver in the arterial phase at 4 months post-radioembolization demonstrates a complete lack of contrast enhancement within the VOI (arrow), suggesting a complete response and clinically validates the ⁹⁰Y PET quantification.

Figure 7

Patient 17. Non-target ⁹⁰Y activity along the gastric greater curve causing CTCAE grade 3 toxicity [1]. A ⁹⁰Y PET VOI of the activity along the gastric greater curve was defined by volumetric isocontour thresholding, visually constrained to its CT anatomical margins, shown here in (a) trans-axial, (b) coronal, and (c) sagittal planes. Within this VOI, the mean ⁹⁰Y radioconcentration at the time of scan (813.1k Bq/ml) was decay-corrected back to the time of ⁹⁰Y radioembolization (1,021.5 kBq/ml). By ⁹⁰Y MIRD macrodosimetry, the non-target mean absorbed dose to the gastric greater curve was approximately 49 Gy within the VOI. Gastroscopy and biopsy findings were reported in part 1 [1].