RT Journal Article
SR Electronic
T1 First-in-human studies characterizing a poly(ADP-ribose)polymerase (PARP) targeted tracer, 18F-FluorThanatrace (18F-FTT) for cancer imaging
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 582
OP 582
VO 57
IS supplement 2
A1 Delphine Chen
A1 Samantha Dyroff
A1 Loren Michel
A1 Andrea Wang-Gillam
A1 Benjamin Tan
A1 Sharon Phillips
A1 Christopher Bognar
A1 Wenhua Chu
A1 Dong Zhou
A1 Robert Mach
A1 Frank Brooks
A1 Richard Laforest
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/582.abstract
AB 582Objectives Poly(ADP-ribose)polymerase (PARP) inhibitors are an emerging therapeutic class of anticancer drugs with the potential to treat cancers that are deficient in DNA repair machinery. We have developed a novel PET imaging tracer, 18F-FluorThanatrace (18F-FTT), that can quantify PARP enzyme activity in vivo. We report the first-in-human studies characterizing the dosimetry for 18F-FTT.Methods Eight healthy volunteers and eight participants with various cancer diagnoses underwent whole body PET/CT imaging at two of the following time points after injecting approximately 370 MBq of 18F-FTT: 0, 30, 60, 90, 120, 150, 180, or 210 min. Any urine excreted in between the two imaging sessions was collected, counted on a gamma counter and used to determine the total amount of activity excreted in the urine in addition to the measured urine activity in the bladder from the images. Volumes of interest were drawn over all visible organs to determine the percent of the injected dose and organ residence times calculated by numerical integration of the time activity data fitted with multi-exponential functions. Residence times were entered into OLINDA/EXM to calculate the organ absorbed doses and effective dose estimates for the adult male and female models.Results The participants with cancer who had measurable disease had diagnoses of mucinous colorectal cancer, pancreatic adenocarcinoma, or biphenotypic hepatocellular carcinoma/cholangiocarcinoma. The liver and spleen as well as normal lymph nodes and the skeleton were easily visualized. Early hepatobiliary excretion of the tracer into the bowels was clearly evident on all images. Renal excretion of the tracer occurred to a lesser extent, as evidenced by a smaller amount of activity in the urinary bladder, which was not consistently visualized in all images. All dose estimates were higher using the female model. The spleen was the critical organ with the highest absorbed dose (0.054 mGy/MBq from the female model), followed by the pancreas (0.048 mGy/MBq from the female model). The effective doses from the male and female models were 0.014 and 0.019 mGy/MBq, respectively. The tumors with the highest uptake were a recurrent pancreatic adenocarcinoma and the biphenotypic hepatocellular carcinoma/cholangiocarcinoma. However, the maximum standard uptake value in the pancreatic adenocarcinoma recurrence was similar to that seen in the normal pancreas in other volunteers. Mucinous colorectal tumors demonstrated mildly increased peripheral uptake with some heterogeneous activity, also of mild intensity, within the mucinous components that correlated with areas of increased density.Conclusions 18F-FTT has favorable characteristics for imaging in humans and may visualize pancreatic and liver cancers particularly well. This tracer may be useful for studying PARP levels and serving as a predictive marker of responsiveness to PARP inhibitor treatment in cancer patients.