<b>Yttrium Radioisotope Impregnated Microspheres  & Liver Metastasis 
Selected Medical Journal Annotated Citations</b> 
[For the full abstract, use the links provided, or search on Pubmed.  Ed.] 


1: Eur J Nucl Med Mol Imaging. 2002 Jun;29(6):815-20. Epub 2002 Mar 29.
!Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI.</b>
Wong CY, Salem R, Raman S, Gates VL, Dworkin HJ.
Department of Nuclear Medicine, William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak, MI 48073-6769, USA. owong@beaumont.edu 

The purpose of this prospective study was to evaluate yttrium-90 glass microsphere treatment of unresectable liver metastases by ...([18F]FDG PET), and to compare the effectiveness of ... PET for this purpose with that of computed tomography (CT) or magnetic resonance imaging (MRI) and determination of the serum carcinoembryonic antigen (CEA) level. 
Thirteen hepatic lobes from eight consecutive patients with colorectal cancer referred for 90Y-glass microsphere treatment of unresectable liver metastases who underwent both baseline (pretreatment) and 3-month posttreatment PET were studied. ...Following treatment, serum CEA decreased significantly, correlating with PET but not with CT or MRI. Thus, the study demonstrated a significant difference between the metabolic and the anatomic response after 90Y-glass microsphere treatment for unresectable liver metastases in colorectal cancer. PET appears to be an accurate indicator of treatment response. Clinical Trial 
&&url PMID: 12029557 


2: Semin Oncol. 2002 Apr;29(2):152-9. 
<b>Radioembolization for hepatic metastases. </b>
Herba MJ, Thirlwell MP. 
Departments of Diagnostic Radiology and Oncology, McGill University Health Center, Montreal General Hospital, Montreal, Canada. 

In a phase I/II study, 37 patients with metastatic liver disease, predominantly from colorectal cancer (n = 33) were treated between 1986 and 1994 by intrahepatic arterial embolization of radioactive yttrium 90 (Y 90) glass microspheres. The calculated total liver dose increased in stages from 5,000 cGy to 15,000 cGy. Mean follow-up was 8 months (range, 1 to 49). No major procedural, hematologic, or pulmonary complications occurred. ...Complications are low and if the tumor pattern is nodular with some hypervascularity, beneficial effects are observed clinically and on imaging studies. Copyright 2002, Elsevier Science (USA). All rights reserved. 
&&url PMID: 11951213 


3: Nucl Med Biol. 1999 Jan;26(1):149-57. 
<b>Treatment of lung tumor colonies with 90Y targeted to blood vessels: comparison with the alpha-particle emitter 213Bi. </b>
Kennel SJ, Stabin M, Yoriyaz H, Brechbiel M, Mirzadeh S. 
Life Sciences Division, Oak Ridge National Laboratory, TN 37831-6101, USA. sj9@ornl.gov 

An in vivo lung tumor model system for radioimmunotherapy of lung metastases was used to test the relative effectiveness of the vascular- targeted beta-particle emitter 90Y, and alpha-particle emitter, 213Bi. Yttrium-90 was shown to be stably bound by CHXa" DTPA-MAb 201B conjugates and delivered efficiently to lung tumor blood vessels. Dosimetry calculations indicated that the lung received 16.2 Gy/MBq from treatment with 90Y MAb 201B, which was a sevenfold greater absorbed dose than any other organ examined. Therapy was optimal for 90Y with 3 MBq injected. ... Yttrium-90 was found to be slightly more effective against larger tumors than 213Bi, consistent with the larger range of 2 MeV beta particles from 90Y than the 8 MeV alpha particles from 213Bi. Treatment of EMT-6 tumors growing in immunodeficient SCID mice with 90Y or 213Bi MAb 201 resulted in significant destruction of tumor colonies; however, 90Y MAb 201B was toxic for the SCID mice, inflicting acute lung damage. In another tumor model, IC-12 rat tracheal carcinoma growing in SCID mouse lungs, 90Y therapy was more effective than 213Bi at destroying lung tumors. However, 90Y MAb 201B toxicity for the lung limited any therapeutic effect. We conclude that, although vascular-targeted 90Y MAb can be an effective therapeutic agent, particularly for larger tumors, in this model system, acute damage to the lung may limit its application. 
&&url PMID: 10096515 

4: Br J Radiol. 1997 Aug;70(836):823-8. 
Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin. 
Ho S, Lau WY, Leung TW, Chan M, Chan KW, Lee WY, Johnson PJ, Li AK. 
Department of Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. 

<b>The selective delivery of a high dose of radiation to malignant hepatic tumours by infusion of non-biodegradable yttrium-90 (90Y) microspheres via the hepatic artery while sparing the non-tumorous liver parenchyma depends on the tumour-to-normal uptake ratio (T/N) of the therapeutic radiopharmaceutical.</b> Using intrahepatic arterial technetium-99m macroaggregated albumin (99Tcm-MAA), the effect of tumour type, tumour vascularity assessed by hepatic angiography (HAG), tumour size and the degree of extrahepatic shunting on the T/N was investigated in 377 patients with hepatocellular carcinoma (HCC) and 25 patients with colorectal liver metastases. ... Overall there was no correlation between T/N and tumour size. Large tumours (> 20 cm) had a significantly lower T/N, probably due to necrosis in the tumour centres. <b>A decrease in mean T/N with increasing percentages of lung shunting was observed in HCC. Determination of T/N by simulation with 99Tcm-MAA is recommended before internal radiation therapy with 90Y microspheres.</b> 
&&url PMID: 9486047 


5: J Nucl Med. 1996 Jun;37(6):958-63. 
Comment in: J Nucl Med. 1996 Jun;37(6):963-4. J Nucl Med. 1997 Jul;38(7):1169-70. 
<b>Ultrasound-guided internal radiotherapy using yttrium-90-glass microspheres for liver malignancies. </b>
Tian JH, Xu BX, Zhang JM, Dong BW, Liang P, Wang XD. 
Department of Nuclear Mecicine, The Great Wall Hospital, Beijing, China. 

Treatment of liver malignancies ... remains a serious problem because of the difficulty of delivering adequate therapeutic agents to the lesions while sparing the surrounding normal tissue. In an attempt to overcome this obstacle, intratumoral injection of 90Y, a beta-emitter, was performed.

... Twenty-seven hepatocellular carcinomas and six liver metastases were studied, most of which had failed other therapeutic modalities. Guided by ultrasound, 90Y-glass microspheres (GMS) were carefully injected into predetermined tumor sites. The procedure was repeated at 3--4-wk intervals where indicated. Echographic, clinical and laboratory follow-up was conducted at regular intervals. RESULTS: Twelve to 32 mo after treatment, 27 patients were still alive, with dramatic improvement of their clinical condition: 90.6% of the tumor foci became smaller, with echogenic or blood flow changes on liver sonograms. ... Repeat biopsy in nine patients showed complete tumor destruction in eight. Six patients died of either end-stage disease or wide dispersion of the tumor. 
...The intratumoral administration of 90Y-GMS under ultrasound guidance yielded a higher cure rate for liver malignancy with no severe side effects. The higher radiation dosage delivered by injected 90Y to the periphery of the lesions (up to 28,215-75,720 cGy) was thought to account for the successful outcome. These results show that intratumoral radionuclide injection is feasible for treatment of malignant lesions inside the body. 
&&url PMID: 8683320 


6: Br J Cancer. 1995 Feb;71(2):322-5. 
<b>Adjuvant internal radiation therapy in a model of colorectal cancer-derived hepatic metastases. </b>
Burton MA, Gray BN. 
School of Science and Technology, Charles Sturt University, Wagga Wagga, Australia. 

Selective internal radiation therapy (SIR therapy) is a technique whereby metastatic liver cancer is irradiated by embolising microspheres containing the radionuclide yttrium-90 into the hepatic arterial circulation. To date this technique has [been used] ... to treat established metastases in the liver. 

<b>This study evaluated the use of two intrahepatic radiation doses delivered on radioactive microspheres for the treatment of small, growing micrometastases. </b>Three groups of five rats were each inoculated with tumour spheroids into the portal vein. The resultant liver micrometastases were treated with either 10 or 20 MBq of yttrium-90 microspheres or a sham dose of non-radioactive microspheres injected into the portal vein 2 days following tumour inoculation. ... These results indicate a potential role for SIR therapy in an adjuvant setting with colorectal cancer. 
&&url PMID: 7841048 


7: Radiother Oncol. 1992 Oct;25(2):137-9. 
<b>Glass yttrium-90 microspheres for patients with colorectal liver metastases. </b>
Anderson JH, Goldberg JA, Bessent RG, Kerr DJ, McKillop JH, Stewart I, Cooke TG, McArdle CS. 
University Department of Surgery, Royal Infirmary, Glasgow, UK. 

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. ... 
&&url PMID: 1438931 


8. Aust N Z J Surg. 1992 Feb;62(2):105-10. 
<b>Regression of liver metastases following treatment with yttrium-90 microspheres. </b>
Gray BN, Anderson JE, Burton MA, van Hazel G, Codde J, Morgan C, Klemp P. 
University Department of Surgery, Royal Perth Hospital, Western Australia. 

<b>Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases.</b> The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. ... SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer. 
&&url PMID: 1586298 


9. J Surg Oncol. 1989 Nov;42(3):192-6. 
<b>Selective internal radiation (SIR) therapy for treatment of liver metastases: measurement of response rate. </b>
Gray BN, Burton MA, Kelleher DK, Anderson J, Klemp P. 
University Department of Surgery, Royal Perth Hospital Perth, Western Australia. 

Ten patients with liver metastases from primary tumors in the colorectum were treated with selective internal radiation (SIR) therapy. This involved the embolisation of yttrium-90-containing microspheres into the hepatic artery at the time of laparotomy. The microspheres were concentrated in the microvasculature of the tumour nodules by the concurrent administration of angiotensin II. The radiation dose being delivered to liver parenchyma was measured at the time of operation by use of an intraoperative radiation detection probe. All nine patients in whom the preoperative carcinoembryonic antigen (CEA) level was elevated experienced a decrease in CEA levels posttreatment. Intraoperative dosimetry confirmed the poor correlation between total radioactivity used and radiation dose received by normal liver parenchyma. 
&&url PMID: 2811384 


10: Can Assoc Radiol J. 1989 Aug;40(4):206-10. 
<b>Treatment of liver tumors with yttrium-90 microspheres alone. </b>
Blanchard RJ, Morrow IM, Sutherland JB. 
Department of Surgery, University of Manitoba, Winnipeg. 

Fifteen patients with liver metastases and one patient with hepatoma were treated by infusing 15 microns diameter plastic microspheres containing yttrium-90 into the hepatic artery. Twenty additional patients were screened but were found to be unsuitable for treatment. Follow-up angiography was done in 13 of the 16 treated patients. In five patients there was a reduction in tumor volume by more than 50% and in another two patients there was a smaller reduction. In six patients gastritis or gastric ulceration occurred and in three this was demonstrated to be due to unintended infusion of microspheres into the gastric circulation. <b>For patients treated with yttrium-90 microspheres, mean survival time after referral was 62 weeks and in the untreated group it was 30 weeks, although this difference was not significant. We conclude that yttrium-90 microspheres alone can effect reduction in the size of liver tumors in some patients in whom their use is feasible. </b>
&&url PMID: 2766018 


11: Cancer Chemother Pharmacol. 1989;23 Suppl:S68-73. 
<b>Hepatic arterial chemotherapy for primary and metastatic liver cancers. </b>
Ensminger W. 
Department of Medicine, University of Michigan Medical School, Ann Arbor. 

Hepatic arterial chemotherapy represents a means of selectively exposing hepatic tumor to cytotoxic agents. Although 5-fluoro-2'-deoxyuridine has been shown to generate a higher response rate in the treatment of colorectal liver metastases than that achieved by intravenous infusion, responses are largely incomplete and rarely of long duration. This review describes the rationale for the use of the thymidine analogs 5-bromo-2'-deoxyuridine and 5-iodo-2'-deoxyuridine in hepatic arterial infusions and indicates how combination therapy adding radiotherapy, specifically with hepatic arterially administered yttrium-90 microspheres, might generate a new, more efficient and effective therapeutic approach. 
&&url PMID: 2647314 


12: J Surg Res. 1983 Jan;34(1):17-24. 
<b>Internal radiotherapy for hepatic metastases I: The homogeneity of hepatic arterial blood flow. </b>
Stribley KV, Gray BN, Chmiel RL, Heggie JC, Bennett RC. 

Internal radiotherapy, in the form of arterially infused yttrium-90-labeled microspheres, theoretically appears encouraging as a method of treatment for hepatic metastases. Previous investigators have assumed a homogeneous distribution of these microspheres and given dosages of isotope based solely on an estimated liver mass. The purpose of this study has been to establish the homogeneity of isotope distribution in liver substance when 15 micrometers microspheres are arterially injected. This has been done in three mammalian species, with the results expressed as a mean percentage coefficient of variation of 28 +/- 5%. Also demonstrated is the fact that 15 micrometers particles, while not penetrating to the venous circulation, achieve a more homogeneous spread throughout the liver than larger particles. It has been demonstrated that to achieve this maximum homogeneity distribution, 4000 beads/g of liver tissue are required. This equates in the therapeutic situation to a maximum activity of 4 Ci/g of infused microspheres. These results are considered significant in that they indicate criteria necessary to achieve the maximum homogeneity of therapeutic agent within liver substance when it is administered by this method, and will allow confidence limits to be attached to direct in vivo measurement of hepatic irradiation. 
&&url PMID: 6823100 


13: J Surg Res. 1983 Jan;34(1):25-32. 
<b>Internal radiotherapy for hepatic metastases II: The blood supply to hepatic metastases. </b>
Stribley KV, Gray BN, Chmiel RL, Heggie JC, Bennett RC. 

...Internal radiotherapy in the form of yttrium-90 microspheres infused into the hepatic artery appears to be a promising method of therapy. One criterion required for the success of this treatment is that of a differentially greater arterial supply to tumor as opposed to liver tissue. This arterial hypervascularity of tumor has been demonstrated before. However, some conflict has been reported as to the maintenance of this state as tumor size increases. <b>Using 15 micrometers Cobalt-57 microspheres for studying salivary adenocarcinoma implants in DA rat livers, these experiments have demonstrated a constant blood flow in the tumor periphery of 3.9 times that within the normal hepatic parenchyma, regardless of tumor size. Also demonstrated is a progressive decrease in central tumor arterial blood flow after a tumor diameter of 6 mm has been exceeded. Arterial hypervascularity of liver tissue adjacent to the tumor has been demonstrated while an intermediate zone of liver tissue appeared hypovascular, suggesting the presence of shunting. In three humans with metastatic liver disease, hepatic artery infusion of particulate radiotracer has demonstrated the peripheral tumor hypervascularity and relative central tumor hypovascularity with good correlation obtained with the images of the metastases on conventional colloidal hepatic scintigraphy. This method allows assessment of the patient's suitability for internal radiotherapy by enabling assessment of the tumor vascularity and the degree of potentially dangerous extrahepatic irradiation.</b> 
&&url PMID: 6681644 


14: Dis Colon Rectum. 1979 Sep;22(6):371-5. 
<b>Internal radiation therapy of hepatic cancer. </b>
Grady ED. 

<b>Established cancer in the liver can, in selected patients who have a good arterial circulation in these tumors, be effectively treated by intrahepatic artery radioactive yttrium-90 resin microspheres.</b> Even in unselected patients treated in the last five years by the author, 17 of 25 patients treated have had good objective regression of cancers, improvement of symptoms and prolongation of life. Treatment is relatively simple and associated with few side effects. ...  
&&url PMID: 498890 


15: J Surg Oncol. 1978;10(4):327-36. 
<b>Treatment of symptomatic metastatic cancer to the liver from primary colon and rectal cancer by the intraarterial administration of chemotherapy and radioactive isotopes. </b>
Ariel IM, Padula G. 

Sixty-five patients were referred for treatment with symptoms resulting from metastatic cancer to the liver from the GI tract. ... The first group of 40 patients were subjected to a laparotomy and insertion of a catheter into the hepatic artery and a second group had the catheter inserted percutaneously and a bolus of cancer chemotherapeutic agents injected into the catheter. In both groups, chemotherapy in the form of 5-fluorouracil was supplemented by internal irradiation delivered from the intraarterial administration of Yttrium 90 microspheres. Forty percent of the patients who had an indwelling catheter performed at celiotomy manifested an objective response and in 60% a significant subjective improvement occurred. In the 25 patients whose catheter was inserted percutaneously, the response rate was roughly similar, in that 35% demonstrated an objective response and 65% demonstrated a subjective response.  
&&url PMID: 692139
