To demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose. Fifteen patients were treated with holmium-166 (166Ho) poly(L-lactic acid)-loaded microspheres (Ho-PLLA-MS, mean 484 mg; range 408–593 mg) in a phase I study. Multi-echo gradient-echo MR images were acquired from which R 2 * maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r 2 * of the Ho-PLLA-MS and compared with the administered amount. Quantitative single photon emission computed tomography (SPECT) was used for comparison with MRI regarding the whole liver absorbed radiation dose. R 2 * maps visualised the deposition of Ho-PLLA-MS with great detail. The mean total amount of Ho-PLLA-MS detected in the liver based on MRI was 431 mg (range 236–666 mg) or 89 ± 19 % of the delivered amount (correlation coefficient r = 0.7; P < 0.01). A good correlation was found between the whole liver mean absorbed radiation dose as assessed by MRI and SPECT (correlation coefficient r = 0.927; P < 0.001). MRI-based dosimetry for holmium-166 radioembolisation is feasible. Biodistribution is visualised with great detail and quantitative measurements are possible. • Radioembolisation is increasingly used for treating unresectable primary or metastatic liver tumours. • MRI-based intrahepatic microsphere biodistribution assessment is feasible after holmium-166 radioembolisation. • MRI enables quantification of holmium-166 microspheres in liver in a short imaging time. • MRI can estimate the whole liver absorbed radiation dose following holmium-166 radioembolisation.
Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 (90Y) microspheres, or iodine-131 (131I) or rhenium-188 (188Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas 90Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when 90Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially 188Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 (166Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since 166Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging.
A potential limitation of rhenium-186-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) therapy in patients with painful bone metastases is thrombocytopenia. Given the palliative character of this therapy, it is essential to be able to predict the degree of thrombocytopenia before therapy.Thus far, 39 prostatic cancer patients with multiple painful bone metastases were treated. Twenty-one patients underwent the therapy twice, resulting in 60 therapies. From the pre-therapy 99mTc-HDP scintigram, the bone scan index (BSI) was determined as an index of the extent of bone involvement.The administered activity ranged from 1104 to 3479 MBq 186Re-HEDP. The platelet count was lowest 4 wk following therapy. From this value and the pretreatment level, the percentage decrease in the platelet count was determined (47% +/- 19%, range 14%-89%). The BSI ranged from 8 to 93. Regression analysis showed a functional relation (R = 0.78; p < 0.001) of the percentage of platelet decrease with BSI and administered activity normalized to standard body surface area.Using this relation, it is possible to predict thrombocytopenia by pretreatment bone scintigraphy and to adjust the dosage to each patient to avoid unacceptable toxicity.
(186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain.Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up.Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.
The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an intravascularly placed catheter.Microspheres were prepared by solvent evaporation, using holmium acetylacetonate (HoAcAc) crystals as the sole ingredient. Microspheres were characterized using light and scanning electron microscopy, coulter counter, titrimetry, infrared and Raman spectroscopy, differential scanning calorimetry, X-ray powder diffraction, magnetic resonance imaging (MRI), and X-ray computed tomography (CT).Microspheres, thus prepared displayed a smooth surface. The holmium content of the HoAcAc microspheres (44% (w/w)) was higher than the holmium content of the starting material, HoAcAc crystals (33% (w/w)). This was attributed to the loss of acetylacetonate from the HoAcAc complex, during rearrangement of acetylacetonate around the holmium ion. The increase of the holmium content allows for the detection of (sub)microgram amounts of microspheres using MRI and CT.HoAcAc microspheres with an ultra-high holmium content were prepared. These microspheres are suitable for radioablation of tumors by intratumoral injections or treatment of liver tumors through transcatheter administration.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmino acid sequence of phosvitin derived from the nucleotide sequence of part of the chicken vitellogenin geneB. Marion Byrne, Alfred D. Van het Schip, Jos A. M. Van de Klundert, Annika C. Arnberg, Max Gruber, and Geert AbCite this: Biochemistry 1984, 23, 19, 4275–4279Publication Date (Print):September 11, 1984Publication History Published online1 May 2002Published inissue 11 September 1984https://pubs.acs.org/doi/10.1021/bi00314a003https://doi.org/10.1021/bi00314a003research-articleACS PublicationsRequest reuse permissionsArticle Views392Altmetric-Citations116LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
