66Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [66Ga]Ga-NOTA-PEG2-RM26

Abstract

Molecular imaging of the gastrin-releasing peptide receptor (GRPR) could improve patient management in prostate cancer. This study aimed to produce gallium-66 (T½ = 9.5 h) suitable for radiolabeling, and investigate the imaging properties of gallium-66 labeled GRPR-antagonist NOTA-PEG2-RM26 for later-time point PET-imaging of GRPR expression. Gallium-66 was cyclotron-produced using a liquid target, and enriched [66Zn]Zn(NO3)2. In vitro, [66Ga]Ga-NOTA-PEG2-RM26 was characterized in GRPR-expressing PC-3 prostate cancer cells. In vivo, specificity test and biodistribution studies were performed 3 h and 22 h pi in PC-3 xenografted mice. microPET/MR was performed 3 h and 22 h pi. Biodistribution of [66Ga]Ga-NOTA-PEG2-RM26 was compared with [68Ga]Ga-NOTA-PEG2-RM26 3 h pi. [66Ga]Ga-NOTA-PEG2-RM26 was successfully prepared with preserved binding specificity and high affinity towards GRPR. [66Ga]Ga-NOTA-PEG2-RM26 cleared rapidly from blood via kidneys. Tumor uptake was GRPR-specific and exceeded normal organ uptake. Normal tissue clearance was limited, resulting in no improvement of tumor-to-organ ratios with time. Tumors could be clearly visualized using microPET/MR. Gallium-66 was successfully produced and [66Ga]Ga-NOTA-PEG2-RM26 was able to clearly visualize GRPR-expression both shortly after injection and on the next day using PET. However, delayed imaging did not improve contrast for Ga-labeled NOTA-PEG2-RM26.

The Use of a Non-Conventional Long-Lived Gallium Radioisotope 66Ga Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule

“…Gallium-66 ( 66 Ga) was produced using the 66 Zn(p,n) 66 Ga reaction by irradiating isotopically enriched (99.07%) 66 Zn target with 14.3 MeV protons, as described earlier [41] with 1 M [ 66 Zn]Zn(NO 3 ) 2 in 0.3 M HNO 3 as a target material. Irradiations (70-75 min,~25 µA) were performed with a GE PETtrace cyclotron (GE Healthcare, Uppsala, Sweden) using a liquid target developed for a cyclotron production of 68 Ga.…”

“…Irradiations (70-75 min,~25 µA) were performed with a GE PETtrace cyclotron (GE Healthcare, Uppsala, Sweden) using a liquid target developed for a cyclotron production of 68 Ga. Separation of [ 66 Ga]GaCl 3 was performed using the GE FASTlab Developer platform using methodology developed for 68 Ga purification [41]. The product was collected here in several 300 µL fractions and the eluate with the highest radioactivity concentration was used for labelling.…”

“…The use of a 66 Ga-labelled somatostatin analogue as an imaging agent for somatostatin receptor positive tumors has also been reported [40]. Recently, first preclinical imaging of GRPR-expression in prostate cancer using [ 66 Ga]Ga-NOTA-PEG2-RM26 has been reported [41].…”

GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

“…[ 68 Ga]Ga-RM26 radiopharmaceuticals which are distinct from each other by radiochemical differences regarding for example the used linkers were developed and evaluated preclinically [22,23,74,76,110].…”

“…Since then, the use of radiolabeled BBN derivatives was investigated in various entities like gastrointestinal stromal tumors, glioma, optic pathway glioma, medullary thyroid, colorectal, breast, and prostate cancer [20,22,23,27,28,29,30,33,34,35,36,37,38,40,41,42,43,44,45,46,47,48,49,50,51,52,54,55,56,57,58,59,60,61,62,63,64,65,67,68,69,70,71,72,73,74,75,76,77,78,79,…”