In vivo characterization of I-123/125-2-iodo-L-phenylalanine in an RIM rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT
Kersemans, V × Cornelissen, B Kersemans, K Bauwens, Matthias Achten, E Dierckx, RA Mertens, J Slegers, G #
Soc nuclear medicine inc
Journal of nuclear medicine vol:46 issue:3 pages:532-539
The application of 123\-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125\-2-iodo-(L)-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates (123)\-2-iodO-(L)-phenylalanine as a new specific tumor tracer for SPECT. Methods: (123/125)\-2-lodO-(L)-phenylalanine is prepared as a one-pot kit using the Cu1+ assisted isotopic exchange method. The characteristics of (125)\-2-iodO-(L)-phenylalanine were examined in vivo in R1M tumor-bearing athymic mice and in acute inflammation-bearing NMRI mice. The uptake of 123/125\-2-iodO-(L)-phenylalanine in tumor and other organs of interest was measured by dynamic planar imaging (DPI) and gamma-counting after dissection. Displacement of (123)\-2-iodO-(L)-phenylalanine radioactivity by L-phenylalanine, L-methionine, and L-cysteine was measured. 123\-lodo-human serum albumin planar imaging was performed to correct for blood-pool activity and MRI was performed to delineate the tumor in DPI. F-18-FDG uptake was measured with an animal PET scanner. (125)\-2-lodo-(L)-phenylalanine and F-18-FIDG uptake in inflamed muscle were compared. Results: 123/125\-2-lodo-(L)-phenylalanine showed a high and fast tumor uptake and followed a reversible first-order pattern allowing calculation of the half-life and the time to reach equilibrium (t(R)). Net tumor-to-background ratios up to 6.7 at 60 min were obtained. This radioactivity was significantly displaced by L-phenylalanine, L-methionine, and L-cysteine, pointing to reversible LAT transport. When plotting tR of the tumor uptake as a function of tumor volume, a rectangular hyperbolic curve was obtained. The almost constant tR values at higher tumor volumes (>4 mL) could be linked to increased necrotic tissue. Fast blood clearance of the tracer through the kidneys to the bladder and low tracer activity in the abdomen and brain were observed. The inflamed muscle showed only a slight increase of (125)\-2-iodo-(L)-phenylalanine uptake (inflammation-to-background ratio, RIB = 1.30 +/- 0.02), in contrast to the high 18F-FDG uptake (RIB = 11.1 +/- 1.7). The in vivo stability of 123/125\-2-iodo-(L)-phenylalanine was good: Only 7% of free radio-iodide and no other labeled metabolites were observed after 90 min. Conclusion: 123/125\-2-lodo-(L)-phenylalanine is quickly taken up by the overexpressed LAT1 system in R1M tumors with high tumor specificity. The availability of a kit and the specificity of the tracer make (123)\-2-iodo-(L)-phenylalanine a promising tool for oncologic SPECT.