Relationship of 99m Technetium Labelled Macroaggregated Albumin (99mTc-MAA) Uptake by Colorectal Liver Metastases to Response Following Selective Internal Radiation Therapy (SIRT)

Abstract and Background

Background: SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of ⁹⁰Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of ⁹⁰Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response.
Methods: 58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT.
Results: Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r² = 0.004). CT responses after 3 months were not different in the 2 Groups.
Conclusion: The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of ⁹⁰Y microspheres used may be greater than is necessary.

Colorectal cancer (CRC) is a particularly common cancer encountered worldwide. Although the primary site is resectable in the majority of instances, metastatic disease will be present or develop in some 50% of those affected within 5 years of presentation. As a result of the portal venous route of spread, the liver is the commonest site of metastases and is frequently the only evident site.^[1] This feature of CRC, coupled with the disappointing results achieved with systemic chemotherapy, has lead to interest in the development of effective regional liver therapies. Such regional approaches include liver resection, cryotherapy or radiofrequency ablation, regional chemotherapy and selective internal radiation therapy (SIRT).

SIRT has been shown to be a particularly effective form of local treatment of CRC liver metastases even when large volumes of tumour are present in multiple sites.^[2,3] It involves selective delivery to tumours of a high dose of ionising radiation achieved by injecting ⁹⁰Yttrium microspheres directly into the hepatic artery. The microspheres, because of their size (25-35 μm) become trapped in capillary beds and preferential uptake into tumour tissue is achieved because of the predominant arterial blood flow to liver tumours relative to normal liver parenchyma.^[4] Radiation dosing is therefore non-homogeneous and the precise dose received will vary within tumour and normal liver tissue and from patient to patient. However average doses received by tumour and normal liver tissue have been calculated to be 200-300Gy and 15-25Gy respectively.^[5] A supra-lethal dose of radiation is therefore received by much of and occasionally all of the tumour, while the dose received by the normal liver tissue is insufficient to result in clinically relevant radiation hepatitis. We and others have shown that fewer than 10% of patients with CRC liver metastases will not respond to this form of treatment based on serial CT scanning and tumour marker (CEA) data.^[2,3] While definitive evidence of extended survival is not yet available, all data point strongly to some survival advantage, at least for those who do not develop extrahepatic disease at an early stage.^[2,6] Selection of those patients most suitable for this form of treatment might be aided by development of a test capable of predicting liver tumour response after SIRT.

^99mTc-MAA scans are routinely advised and performed prior to SIRT to confirm access to all areas of the liver from the hepatic artery and isolation of the liver from other foregut structures.^{[7] 99m}Tc-MAA has a "particle" size (10-60 μm, average 35 μm) similar to the resin microspheres used for SIRT and can therefore be used as a tracer dose to indicate approximate distribution of ⁹⁰Yttrium microspheres to be expected during SIRT. Tumours with high ^99mTc-MAA uptake can be expected to receive a high dose of ⁹⁰Yttrium microspheres and it seems possible they may respond correspondingly better than tumours demonstrating low uptake of ^99mTc-MAA. This hypothesis has not previously been thoroughly tested. There have however been contradictory reports regarding the association between ^99mTc-MAA uptake by hepatic tumours and response after hepatic artery chemotherapy (HAC).^[8,9,10,11] The purpose of this study was to determine whether the pattern of uptake of ^99mTc-MAA after arterial injection, by colorectal liver metastases is predictive of tumour response after SIRT.

BMC Nucl Med. 2005;5 © 2005  Dhabuwala et al; licensee BioMed Central Ltd.
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Cite this: Relationship of 99m Technetium Labelled Macroaggregated Albumin (99mTc-MAA) Uptake by Colorectal Liver Metastases to Response Following Selective Internal Radiation Therapy (SIRT) - Medscape - Dec 23, 2005.