MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation

Maat, Gerrit H. van de; Seevinck, Peter R.; Elschot, Mattijs; Smits, Maarten L. J.; Leeuw, Hendrik de; Schip, Alfred D. van het; Vente, M. A. D.; Zonnenberg, Bernard A.; Jong, Hugo W. A. M. de; Lam, Marnix G. E. H.; Viergever, Max A.; Bosch, Maurice A.A.J. van den; Nijsen, J. Frank W.; Bakker, Chris J.G.

doi:10.1007/s00330-012-2648-2

Cited by 67 publications

(60 citation statements)

References 29 publications

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“…Although spatial resolution, contrast recovery, and sensitivity are worse for 166 Ho than 99m Tc-MAA, injection of 250 MBq of 166 Ho microspheres is sufficient to provide images that allow for the evaluation of lung shunt and extrahepatic deposition (24,25). Another benefit of 166 Ho microspheres, and a principal reason for their development (26), is the possibility of their multimodal detection: an 81-keV photopeak for nuclear imaging (24), high magnetic susceptibility for MR imaging (27), and a high mass attenuation coefficient for CT imaging (28). The most promising modality, MR imaging, could enable MR-guided treatment, as has been performed ex vivo in rabbits (29).…”

Section: Discussionmentioning

confidence: 99%

Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

et al. 2015

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Before 166 Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional 99m Tc-macroaggregated albumin ( 99m Tc-MAA). The 166 Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to 99m Tc-MAA, an unintended extrahepatic deposition of this β-emitting scout dose could inflict radiation damage, the extent of which we aimed to quantify in this study. Methods: All patients eligible for radioembolization in our institute between January 2011 and March 2014 were reviewed. Of the extrahepatic depositions of 99m Tc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a 166 Ho scout dose had been used. The extrahepatic activity was measured as the sum of all voxels of the deposition. Volumes were measured using a threshold technique including all voxels from the maximum voxel intensity up to a certain percentage. The threshold needed to obtain the true volume was studied in a phantom study. Results: In the phantom study, a threshold of 40% was found to overestimate the volume, with the consequence of underestimating the absorbed dose. Of 160 patients, 32 patients (34 cases) of extrahepatic deposition were identified. The depositions contained a median of 1.3% (range, 0.1%-19.5%) of the administered activity in a median volume of 6.8 mL (range, 1.1-42 mL). The use of a scout dose of 250 MBq of 166 Ho microspheres in these cases would theoretically have resulted in a median absorbed dose of 6.0 Gy (range, 0.9-374 Gy). The dose exceeded a limit of 49 Gy (reported in 2013) in 2 of 34 cases (5.9%; 95% confidence interval, 0.7%-20.1%) or 2 of 160 (1.3%; 95% confidence interval, 0.1%-4.7%) of all patients. In these 2 patients with a large absorbed dose (112 and 374 Gy), the culprit vessel was identified in 1 case. Conclusion: Extrahepatic deposition of a 166 Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials. Radi oembolization is a minimally invasive treatment for hepatic malignancies. Millions of radioactive microspheres are injected in the hepatic artery to radiate and embolize malignancies (1). Deposition of microspheres in gastrointestinal organs can result in ulceration or inflammation of tissue by a combination of embolization and radiation damage (2-4). To prevent this, vessels leading to gastrointestinal organs may be coil-embolized in patients scheduled for radioembolization treatment, during a pretreatment session using contrastenhanced images (i.e., digital subtraction angiography complemented by C-arm CT) to identify the culprit vessel (5). 99m Tc-macroaggregated albumin ( 99m Tc-MAA) is administered in this pretreatment session to simulate intrahepatic treatment biodistribution and to assess lung shunting and the possibility of extrahepatic deposition of the microspheres (6). This procedure is safe because 99m Tc-MAA emits 140-keV g photons (detecta...

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Section: Discussionmentioning

confidence: 99%

Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

et al. 2015

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“…MR imaging-based absorbed dose maps were generated using previously described and validated methods (8,19). In short, R 2 * values were estimated voxelwise from the multi-gradient echo data using a monoexponential fitting algorithm weighting all signal amplitudes equally.…”

Section: Quantitative Analysis and Dosimetrymentioning

confidence: 99%

“…To determine the microsphere-induced change in R 2 * (DR 2 *) after therapy, a baseline R 2 * value was subtracted from the posttherapy R 2 * values. This baseline value was, in contrast to the previously described method (19), determined for each VOI separately by the mean R 2 * value of that VOI before therapy. Voxelwise concentrations of 166 Ho-microspheres were determined from the DR 2 * maps by the relationship [ 166 Ho-microspheres] 5 DR 2 */r 2 *, with r 2 * 5 103 s 21 mL 21 mg for 166 Ho-microspheres with holmium content of 18.9% by weight (19).…”

Section: Quantitative Analysis and Dosimetrymentioning

confidence: 99%

“…This baseline value was, in contrast to the previously described method (19), determined for each VOI separately by the mean R 2 * value of that VOI before therapy. Voxelwise concentrations of 166 Ho-microspheres were determined from the DR 2 * maps by the relationship [ 166 Ho-microspheres] 5 DR 2 */r 2 *, with r 2 * 5 103 s 21 mL 21 mg for 166 Ho-microspheres with holmium content of 18.9% by weight (19). The total amount of 166 Ho-microspheres (mg) in each voxel was determined by using the voxel volume.…”

Section: Quantitative Analysis and Dosimetrymentioning

confidence: 99%

“…This amount of 166 Ho-microspheres was then converted into units of activity (MBq) by multiplication by the specific activity of the microspheres. Patients with surgical clips were excluded from analysis of MR imaging dosimetry because it has been demonstrated that MR imaging dosimetry is not reliable in these patients (19).…”

Section: Quantitative Analysis and Dosimetrymentioning

confidence: 99%

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In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies

et al. 2013

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166 Ho-poly(L-lactic acid) microspheres allow for quantitative imaging with MR imaging or SPECT for microsphere biodistribution assessment after radioembolization. The purpose of this study was to evaluate SPECT-and MR imaging-based dosimetry in the first patients treated with 166 Ho radioembolization. Methods: Fifteen patients with unresectable, chemorefractory liver metastases of any origin were enrolled in this phase 1 study and were treated with 166 Ho radioembolization according to a dose escalation protocol . The contours of all liver segments and all discernible tumors were manually delineated on T2-weighted posttreatment MR images and registered to the posttreatment SPECT images (n 5 9) or SPECT/CT images (n 5 6) and MR imagingbased R 2 * maps (n 5 14). Dosimetry was based on SPECT (n 5 15) and MR imaging (n 5 9) for all volumes of interest, tumor-tonontumor (T/N) activity concentration ratios were calculated, and correlation and agreement of MR imaging-and SPECT-based measurements were evaluated. Results: The median overall T/N ratio was 1.4 based on SPECT (range, 0.9-2.8) and 1.4 based on MR imaging (range, 1.1-3.1). In 6 of 15 patients (40%), all tumors had received an activity concentration equal to or higher than the normal liver (T/N ratio $ 1). Analysis of SPECT and MR imaging measurements for dose to liver segments yielded a high correlation (R 2 5 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, 211.2 to 18.7). Conclusion: With the use of 166 Ho-microspheres, in vivo dosimetry is feasible on the basis of both SPECT and MR imaging, which enables personalized treatment by selective targeting of inadequately treated tumors. Radi oembolization is an interventional oncologic treatment during which radioactive microspheres are administered in the arterial vessels supplying the liver and its tumors. The rationale behind this intraarterial liver treatment is that liver tumors are predominantly supplied by arterial blood, in contrast to the nontumorous liver, which relies mainly on the portal vein for its blood supply. Injection of a substance into the hepatic artery will therefore selectively target the tumorous tissue (1). Currently, the commercially available microspheres that are used for radioembolization are labeled with 90 Y. To be able to quantitatively evaluate the optimal and selective distribution of microspheres to the liver tumors, posttreatment imaging is indispensable. For that reason, optimization of posttreatment imaging of 90 Y-microspheres with bremsstrahlung SPECT and PET has recently gained interest (2-5).166 Ho-poly(L-lactic acid) microspheres have been developed at our institute as an alternative to 90 Y-microspheres specifically to be able to visualize the in vivo biodistribution of microspheres after radioembolization. 166 Ho-microspheres can be imaged with both SPECT and MR imaging, using the emission of g-photon radiation and the paramagnetic properties of holmium, respectively (6-10). Exploiting these qualities, multimodal dosimetry becomes feasible,...

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Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy

et al. 2014

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Resection and radiofrequency ablation (RFA) are treatment options for hepatocellular carcinoma (HCC) <3 cm; there is interest in expanding the role of ablation to 3-5 cm. RFA is considered high-risk when the lesion is in close proximity to critical structures. Combining microcatheter technology and the localized emission properties of Y90, highly selective radioembolization is a possible alternative to RFA in such cases. We assessed the efficacy (response, radiology-pathology correlation, survival) of radiation segmentectomy in solitary HCC not amenable to RFA or resection. Patients with treatment-na€ ıve, unresectable, solitary HCC £ 5 cm not amenable to RFA were included in this multicenter study. Administered dose, response rate, time-to-progression (modified Response Evaluation Criteria in Solid Tumors [mRECIST]), radiology-pathology correlation and long-term survival were assessed. In all, 102 patients were included in this study. mRECIST complete response (CR), partial response (PR), and stable disease (SD) were 47/99 (47%), 39/99 (39%), and 12/99 (12%), respectively. Median time-to-disease-progression was 33.1 months. In all, 33/ 102 (32%) patients were transplanted with a median (interquartile range [IQR]) time-totransplantation of 6.3 months (3.6-9.7). Pathology revealed 100% and 50-99% necrosis in 17/33 (52%) and 16/33 (48%), respectively. Median overall survival was 53.4 months. Univariate analysis demonstrated a survival benefit for Eastern Cooperative Oncology Group (ECOG) 0 patients. In the multivariate model, age <65, ECOG 0, and Child-Pugh A were characteristics associated with longer survival. Conclusion: Radiation segmentectomy is an effective technique with a favorable risk profile and radiology-pathology outcomes for solitary HCC £ 5 cm. This approach may allow for treatment of HCC in difficult locations. Since RFA and resection are not options given tumor location, there appears to be a strong rationale for this technique as second choice. (HEPATOLOGY 2014;60:192-201) H epatocellular carcinoma (HCC) is a health problem of global proportions that has a wide variety of treatment options. Tumor location, size, number of lesions, liver function, and clinical symptoms all play a role in weighing various treatment modalities. Although liver transplantation and resection are considered curative, scarce transplant availability and patient/tumor characteristics limit Abbreviations: AASLD, American Association for the Study of the Liver; AFP, alpha

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MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation

Cited by 67 publications

References 29 publications

Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies

Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy

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MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation

Cited by 67 publications

References 29 publications

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

In Vivo Dosimetry Based on SPECT and MR Imaging of166Ho-Microspheres for Treatment of Liver Malignancies

Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy

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Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

Safety of a Scout Dose Preceding Hepatic Radioembolization with ¹⁶⁶Ho Microspheres

In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies