Page 139 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Albutate-1, a novel long-circulating radiotracer
inoculated subcutaneously with 4 X 106 H69 tumor cells. When a tumor volume of on average 200 mm3 was reached the mice were injected with 30 MBq/240 pmol of [177Lu]Lu-Albutate-1 intravenously via the tail vein. Two minutes prior to this injection 4 mg Gelofusine (B. Braun Medical BV, Oss, The Netherlands) [39] was injected i.v. to reduce renal uptake. Four mice were injected with block; 50 ug Albutate-1, 1 minute prior to an injection with gelofusin and 30 MBq/240 pmol of [177Lu]Lu-Albutate-1. Mice were euthanized at different time points (1, 24, 48, 72 and 168 h, n=4 per time point) post injection (p.i.). Blood, various organs and tumor were collected, weighed and radioactivity contained in the tissue samples was measured in a gamma counter (Wallac, 1480 Wizard 3”, PerkinElmer, Turku, Finland). The percentage injected dose per gram of tissue (%ID/g) was calculated. Mice were housed at the Experimental Animal Facility of the Erasmus MC with a 12 h light–dark regimen, in individually ventilated cages including extensive cage enrichment. The mice received acidified tap water and standard chow ad libitum. In vivo studies with [177Lu]Lu-DOTA-TATE were previously performed at our department [40-43].
4.6. Dosimetry
The biodistribution data for [177Lu]Lu-Albutate-1 was used to determine time- activity curves (TAC) for each organ and the tumor. A single compartment distribution model was assumed for the fit of the TAC data with a bi-exponential curve A(t):
with coefficients for uptake (λupt = ln(2)/Tupt) proceeding with a half-life of Tupt and for clearance (λclr = ln(2)/Tclr), proceeding with a clearance half-life of Tclr. The blood TAC was fitted with a single exponential function. The total number of disintegrations à in each organ was calculated by integration to infinity of the exponential curves multiplied with the 177Lu decay curve. The absorbed doses were determined according to the MIRD equation Dk = ΣhÃh x S(k  h). The S-values for 177Lu in a 22 g mouse were obtained from Monte Carlo calculations in the Realistic Moby phantom [44], kindly provided by Erik Larsson. The blood contents in each bone marrow compartment was determined with the blood TAC and the marrow cellularity according to Colvin et al. [45]. The distribution of the blood à in each marrow compartment was based on the fractional cellularity CBM.
A(t) = Amax (exp(‒λclrt) ‒ exp(‒λuptt))
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