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Endocrine Abstracts (2023) 98 B14 | DOI: 10.1530/endoabs.98.B14

1The University of Chicago, Chicago, IL; 2Argonne National Laboratory, Lemont, IL; 3Oak Ridge National Laboratory, Oak Ridge, TN

Background: Neuroendocrine tumors (NETs) represent a heterogenous group of neoplasms and their diagnosis can be challenging. In 2019, FDA approved 68Gallium labeled DOTATATE PET tracer for SSTR2 overexpressing NETs, which has been widely adopted since. However, limitations of 68Ga-DOTATATE have led to the development of additional radiotracers for the diagnosis of NETs. Herein we report on a novel PET tracer using 43Sc for DOTATATE labeling. 43Sc provides a longer half-life when compared against 68Ga and its lower positron energy provides better quality of PET imaging and less deposit of radiation into non-tumoral tissues.

Methods: 43Sc production was achieved at the University of Chicago Cyclotron Facility through the 42Ca(d,n)43Sc reaction. The radiolabeling was done on a thermomixer at 450 rpm for 30 min at 95°C. The crude was passed through a conditioned C18 SPE cartridge where 43Sc-DOTATATE was trapped and eluted in EtOH. Cellular uptake and internalization studies were conducted using the SSTR2 overexpressing pancreatic NET cells, QGP1-SSTR2 and the parental QGP1 cells served as a negative control. in vivo PET/CT imaging was conducted on male nude mice bearing QGP1 and QGP1-SSTR2 tumor xenograft on the right and left forelimbs respectively. Dynamic PET acquisition started right before the injection of 43Sc-DOTATATE via a tail vein catheter, and followed by CT imaging for anatomy and attenuation correction. Select tissues were collected post-imaging for biodistribution.

Results: Radiolabeling efficiencies were routinely >97%. Specific activity as high as 660 µCi/nmole was achieved with >99% radiochemical purity. The highest SSTR2-QGP1 uptake of >60%AA/105cells was observed at pM level of 43Sc-DOTATATE and ~70% of this activity was internalized. QGP1 cells showed baseline levels of 43Sc-DOTATATE uptake while unlabeled DOTATATE diminished radiotracer uptake in the QGP1-SSTR2 cells. PET imaging revealed that specific uptake of 43Sc-DOTATATE in QGP1-SSTR2 xenografts peaked at 1 hr after IV injection. No signal was observed in QGP1 tumors. The time-activity curve showed a clear separation between surrounding tissues and tumors starting at~30 min post-injection. Biodistribution analyses post-injection confirmed strong tracer localization, ~30 %ID/g, in QGP1-SSTR2 tumors, with substantially lower uptake seen in both the kidneys and QGP1 tumors, 10 and 4 %ID/g, respectively.

Conclusion: Cellular uptake and internalization in SSTR2 overexpressing pNET cells are higher than those in SSTR2-deficient cells, demonstrating 43Sc-DOTATATE labeling was successful with high purity and specific activity. High uptake in QGP1-SSTR2 xenografts indicates that this radiotracer is a promising novel diagnostic agent for the clinical diagnosis of NET malignancies.

Abstract ID 23766

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