Compensating Positron Range Effects of Ga-68 in Preclinical PET Imaging by Using Convolutional Neural Network: A Monte Carlo Simulation Study

This study aimed to investigate the feasibility of positron range correction based on three different convolutional neural network (CNN) models in preclinical PET imaging of Ga-68. The first model (CNN1) was originally designed for super-resolution recovery, while the second model (CNN2) and the third model (CNN3) were originally designed for pseudo CT synthesis from MRI. A preclinical PET scanner and 30 phantom configurations were modeled in Monte Carlo simulations, where each phantom configuration was simulated twice, once for Ga-68 (CNN input images) and once for back-to-back 511-keV gamma rays (CNN output images) with a 20 min emission scan duration. The Euclidean distance was used as the loss function to minimize the difference between CNN input and output images. According to our results, CNN3 outperformed CNN1 and CNN2 qualitatively and quantitatively. With regard to qualitative observation, it was found that boundaries in Ga-68 images became sharper after correction. As for quantitative analysis, the recovery coefficient (RC) and spill-over ratio (SOR) were increased after correction, while no substantial increase in coefficient of variation of RC (CVRC) or coefficient of variation of SOR (CVSOR) was observed. Overall, CNN3 should be a good candidate architecture for positron range correction in Ga-68 preclinical PET imaging.

PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the “Cancer Integrin” αvβ6 with Ga-68-Trivehexin

Purpose To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas. Methods Ga-68-Trivehexin was synthesized by trimerization of the optimized αvβ6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[YRGDLAYp(NMe)K]) on the TRAP chelator core, followed by automated labeling with Ga-68. The tracer was characterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well as by cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID-mice bearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static (75 min p.i.) µPET imaging, as well as for biodistribution (90 min p.i.). Structure–activity-relationships were established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, and metastatic PDAC. Results Ga-68-Trivehexin showed a high αvβ6-integrin affinity (IC50 = 0.047 nM), selectivity over other subtypes (IC50-based factors: αvβ8, 131; αvβ3, 57; α5β1, 468), blockable uptake in H2009 cells, and negligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a high target-specific uptake in tumor and a low non-specific uptake in other organs and tissues except the excretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results, showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10–13) as well as in kidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed high uptake in HNSCC but not in tumor-associated inflammation. Conclusions Ga-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.

PET/CT Imaging of Head-and-Neck and Pancreatic Cancer in Humans by Targeting the "Cancer Integrin" αvβ6 with Ga-68-Trivehexin

PurposeTo develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.MethodsGa-68-Trivehexin was synthesized by trimerization of an optimized αvβ6-integrin selective cyclicnonapeptide on the TRAP chelator core and automated labeling with Ga-68. The tracer wascharacterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well asby cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID micebearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static(75 min p.i.) μPET imaging, as well as for biodistribution (90 min p.i.). Structure-activity-relationshipswere established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, andPDAC.ResultsGa-68-Trivehexin showed a high αvβ6-integrin affinity (IC50 = 0.033 nM), selectivity over othersubtypes (IC50-based factors: αvβ8, 188; αvβ3, 82; α5β1, 667), blockable uptake in H2009 cells, andnegligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a hightarget-specific uptake in tumor and a low non-specific uptake in other organs and tissues except theexcretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results,showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10–13) as well as inkidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed highuptake in HNSCC but not in tumor-associated inflammation.ConclusionsGa-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.