The Precision of Hepatic Arterial Infusion Scintigraphy as a Quantitative Biomarker of Tumor Microvasculature

Abstract

Objective: Optimal clinical development of new cancer therapies targeting tumor vasculature requires new target-specific response assays. This clinical study examined the test-retest repeatability of SPECT as an in vivo assay of angiogenic hepatic tumor microvasculature using an intraarterial infusion of ^99mTc-macroaggregated albumin (MAA) delivered via a hepatic artery infusion (HAI) pump.

Materials and methods: Patients with primary or secondary cancerous liver tumors with HAI pump-catheter implants placed for HAI chemotherapy underwent hepatic SPECT after separate arterial infusions of 37 and 185 MBq of ^99mTc-MAA via an HAI pump. Quantitative measures of hepatic tumor MAA uptake were obtained from paired test-retest SPECT datasets. Repeatability was defined by quotients of paired measurands with 95% CIs and coefficients of repeatability (CRs).

Results: Test-retest HAI pump SPECT yielded highly repeatable measurements in quantitative indexes of tumor microvasculature. Variability in repeat test-retest measurements was small relative to the range of observed measurements between different tumors. The total hepatic tumor microvascular MAA accumulation (percentage injected dose) proved most repeatable, with test-retest value quotients near unity (quotients: median, 1.10 ± 0.09 [SD]; range, 1.03-1.32; 95% CI, 1.07-1.19) and 1.6% CR. Tumor MAA uptake values ranged from 5% to 18% injected dose.

Conclusion: This article describes the precision of HAI SPECT as a quantitative biomarker of tumor microvasculature under conditions of repeatability. The results support clinical testing of HAI SPECT as a radiologic response biomarker for angiotropic tumor therapy.

Keywords: angiogenesis inhibitors; liver neoplasms; microspheres; neovascularization; pathologic neovascularization; yttrium radioisotopes.

Fig. 1

Paired test-retest hepatic arterial infusion (HAI) scintigraphic measurements of hepatic tumor macroaggregated albumin (MAA) uptake quantified as percentage injected dose (%ID) of radiotracer. For each patient (x-axis), tumor microvascular MAA-uptake is plotted (y-axis) as quantified by first SPECT examination (diamonds) and repeat SPECT examination (boxes).

Fig. 2

Hepatic tumors in two patients with colorectal cancer metastases to liver. A–D, Transaxial ^99mTc–macroaggregated albumin (MAA) hepatic arterial infusion (HAI) SPECT image (A) and corresponding axial CT image (B) of 61-year-old man and transaxial ^99mTc-MAA HAI SPECT image (C) and corresponding axial CT image (D) of 42-year-old woman. Dense microvasculature in periphery of hepatic tumors is visualized as rings of concentrated ^99mTc-MAA (arrows, A and C). Tumors show center devoid of ^99mTc-MAA, which is consistent with nonperfused necrotic cores. One patient had small tumor (4.3 × 4.0 cm) (arrow, B); other patient had larger tumor (9.2 × 7.8 cm) (arrows, D). Both tumors had similar total ^99mTc-MAA uptake (tumor percentage injected dose [%ID] values); however, small tumor had higher concentration of ^99mTc-MAA uptake (%ID/cm³) consistent with higher tumor microvessel density.