Science Briefs from the SNMMI Annual Meeting.

Theranostic RIT in CRC Researchers from Memorial Sloan– Kettering Cancer Center (New York, NY) and the Massachusetts Institute of Technology (Cambridge, MA) reported on continuing small animal studies with curative theranostic pretargeted 177LuDOTAT-Bn radioimmunotherapy (PRIT) in GPA33-expressing colorectal cancer. Mice with established SW1222 subcutaneous xenografts underwent treatment with 177Lu-DOTAT-Bn alone, 3 cycles of PRITwith anti-GPA33 PRIT 1 55 MBq of 177Lu-DOTA-Bn per cycle, or no treatment. Serial nanoSPECT/CT in the group undergoing PRIT was used for dosimetry calculations. 177Lu-DOTA-Bn PRIT induced complete tumor response in animals autopsied at 21 d after treatment, with tumor-free survival of all other PRIT animals at 100 d. Histopathology at 100 d showed no remarkable findings in kidney, liver, spleen, or bone/marrow in treated animals. Dosimetry calculations from imaging allowed the authors to estimate total 177Lu radiation exposure to tumor following curative treatment (all 3 cycles) at 14,000 rads, with radiation doses to blood and kidney of 150 rads and 875 rads, respectively. The authors concluded that these theranostic PRIT regimens with a cumulative tumor radiation dose of ;14,000 rads and therapeutic indices of 93 for blood and 16 for kidneys are “safe and sufficient for cure of colorectal cancer.” “If these results can be replicated in prospective human studies, this multiplatform approach could be used with an array of antibodies to treat a number of cancers, especially colorectal and ovarian cancers,” said Sarah M. Cheal, PhD, first author of the study. PET and Brain Changes in Alcohol Dependence Researchers from University Hospital Gasthuisberg (Leuven, Belgium) and colleagues from the University of Leuven and University of Antwerp (Belgium) reported on a study using 18F-FPEB PET imaging to evaluate the role of metabotropic glutamate receptor subtype 5 (mGluR5) signaling in the physiopathology of alcoholdependent individuals. The study included 16 recently abstinent alcoholdependent individuals (ages, 45 6 8 y; range, 32–57 y) and 32 age-matched healthy controls. All participants underwent 18F-FPEB PET imaging and arterial blood sampling. Alcohol use was clinically assessed with self-report questionnaires and ethyl glucuronide hair analysis. Image analyses showed decreased mGluR5 availability in alcoholics in the bilateral cingulate, caudate, and insular cortex, changes not associated with sex or smoking status. Additional analyses showed mean changes in total tracer distribution volumes of –27% 6 4% in the caudate, –26% 6 4% in the insula, –23% 6 5% in the anterior cingulate, and –19% 6 5% in the posterior cingulate in alcohol-dependent individuals compared with controls. mGluR5 binding was also negatively correlated with ethyl glucuronide hair levels in alcohol dependence. The authors concluded that “mGluR5 availability is decreased in the limbic system of alcohol-dependent subjects” and that these data imply “the functional role of mGluR5 in the physiopathology of alcohol addiction.” “Collectively, these findings strongly substantiate the development of mGluR5-targeted therapies that heal or protect against the dysfunctional brain circuitry that characterizes alcohol addiction,” said Gil Leurquin-Sterk, MD, first author of the study.