Representative slice showing positioning of each ROI. ROI 1 (red) is contour over LV for determining partial volume effect correction; ROI 2 (blue) is internal to LV for determining average red marrow activity concentration. Source: J Nucl Med April 1, 2012 (online)

Time-independent proportionality between red marrow and plasma activity concentration may be too simplistic. Individualized imaged-based dosimetry is probably required for the optimal therapeutic delivery of radiolabeled antibodies, which does not compromise red marrow and may allow, for some patients, a substantial increase in administered activity and thus tumor dose, based on a study in the April issue in the Journal of Nuclear Medicine.

“The goal in radioimmunotherapy is to maximize the absorbed dose to target volumes while ensuring that delivery to vulnerable normal organs is within acceptable limits,” according to the study authors. “Typically, for radioimmunotherapy the dose-limiting organ is the red marrow (i.e., the blood-forming cells of the bone marrow).”

In this study, Jazmin Schwartz, PhD, of the department of medical physics at Memorial Sloan-Kettering Cancer Center in New York City, and colleagues estimated red marrow activity concentration and the self-dose component of absorbed radiation dose to red marrow based on PET/CT of two different ¹²⁴I-labeled antibodies (cG250 and huA33) and compared the results with plasma activity concentration and plasma-based dose estimates.

The researchers imaged two groups of patients injected with ¹²⁴I-labeled monoclonal antibodies (11 patients with renal cancer receiving ¹²⁴I-cG250 and five patients with colorectal cancer receiving ¹²⁴I- huA33) with PET or PET/CT on two or three occasions after infusion. Regions of interest (ROI) were drawn over several lumbar vertebrae, and red marrow activity concentration was quantified. Plasma activity concentration was quantified using multiple patient blood samples.

They also calculated red marrow-to-plasma activity concentration ratio (RMPR) at the times of imaging. The self-dose component of the absorbed radiation dose to the red marrow was estimated from the images, from the plasma measurements and using a combination of both sets of measurements.

Schwartz et al observed RMPR increased with time for both groups of patients. Mean time-dependent RMPR (RMPR(t)) for the cG250 group increased from 0.13 immediately after infusion to 0.23 at approximately six days after infusion. For the huA33 group, mean RMPR(t) was 0.10 immediately after infusion, 0.13 approximately two days after infusion and 0.20 approximately seven days after infusion.

Plasma-based estimates of red marrow self-dose tended to be greater than image-based values by, on average, 11 percent and 47 percent for cG250 and huA33, respectively, but by as much as -73 percent to 62 percent for individual patients, the researchers reported. The hybrid method combining RMPR(t) and plasma activity concentration provided a closer match to the image-based dose estimates (average discrepancies, -2 percent and 18 percent for cG250 and huA33, respectively).

“The data presented in this paper indicate that plasma-based dosimetry can produce discrepancies of as much as -74 percent to 62 percent in individual patients for red marrow self-dose due to ¹²⁴I-labeled antibodies, in comparison with PET image–based dosimetry,” concluded the study authors. “Projected differences for other radionuclides between plasma- and appropriate image-based dose estimates would depend on additional factors, including physical half-life and photon yield, but are likely to be of the same order.”

They also wrote that the implication is that individualized imaged-based dosimetry would be optimal for therapeutic delivery of radiolabeled antibodies, both in terms of maximizing radiation dose to target tissues and in terms of remaining within the tolerance of red marrow.

This work was supported by a grant from the National Institutes of Health and by the Ludwig Center for Cancer Immunology at Sloan-Kettering Institute.