Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer

Sevcenco, Sabina; Klingler, H. Christoph; Eredics, Klaus; Friedl, Alexander; Schneeweiss, J; Kabos, Peter; Kunit, Thomas; Lusuardi, Lukas; Mirzaei, Siroos

doi:10.1007/s12325-018-0711-3

Cited by 16 publications

(21 citation statements)

References 14 publications

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“…It is important to underline that the high liver uptake can be associated with transchelation and enzymatic degradation by liver enzymes. Earlier PET studies showed 64 Cu NODAGA-PSMA to be a promising imaging tool to detect residual disease in patients with recurrent or primary progressive prostate cancer (31).…”

Section: Discussionmentioning

confidence: 99%

“…Further examples of previous publications that describe copper-labeled radiotracers for the targeting of PSMA-expressing tumors are 64 Cu-NODAGA-PSMA and 64 Cu-ABN-1. The Maecke group made a comprehensive preclinical comparison of 64 Cu-NODAGA-PSMA to several alternative tracers (30), and subsequently, clinical studies with 64 Cu-NODAGA-PSMA were published (31). As an alternative to the urea-based PSMA-binding tracers, 64 Cu-ABN-1 represents a phosphoramidatebased tracer (32).…”

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confidence: 99%

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Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

et al. 2019

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Prostate-specific membrane antigen (PSMA)-binding tracers have been shown to be promising agents for the specific targeting of prostate tumors. On labeling with the short-lived isotopes 18 F and 68 Ga, excellent molecular imaging performance is achieved. This potential could be further exploited using long-lived isotopes. Because of the favorable half-life of 64 Cu, tracers labeled with this PET nuclide could solve logistic problems. Moreover, this isotope provides a theranostic pair with the therapeutic copper isotope 67 Cu. Hence, 9 novel tracers that combine dedicated copper chelators with the PSMA-specific urea-based binding motif were developed. Methods: The precursors were obtained by solid-phase synthesis. The purity and molecular weight of the PSMA ligands were confirmed by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The compounds were labeled with 64 Cu, with a radiolabeling yield of more than 99%. Competitive cell binding assays and internalization assays were performed with C4-2 cells, a subline of the PSMA-positive cell line LNCaP (human lymph node carcinoma of the prostate). In vitro serum stability, the stability of 64 Cu-CA003 in blood, and the in vivo fate of neat 64 Cuchloride or 64 Cu-CA003 were determined to prove whether the stability of the radiolabeled compounds is sufficient to ensure no significant loss of copper during the targeting process. For PET imaging and biodistribution studies, a C4-2 tumor-bearing mouse model was used. Results: The radiolabeled 64 Cu-PSMA ligands showed high serum stability. All PSMA ligands showed high inhibition potencies, with equilibrium inhibition constants in the low nanomolar range. 64 Cu-CA003 and 64 Cu-CA005 showed high internalization ratios (34.6% ± 2.8 and 18.6% ± 4.4, respectively). Both the in vitro serum stability determination and the in vivo characterization of the main radiolabeled compounds confirmed that, except for 64 Cu-PSMA-617, all compounds showed high serum stability within the observation period of 24 h. Small-animal PET imaging demonstrated high tumor uptake within 20 min. Organ distribution studies confirmed high specific uptake in the tumor, with 30.8 ± 12.6 percentage injected dose (%ID)/g at 1 h after injection. Rapid clearance from the kidneys was observed-a decrease from 67.0 ± 20.9 %ID/g at 1 h after injection to 7.5 ± 8.51 %ID/g at 24 h after injection (in the case of CA003). The performance of CA003, the compound with the best preclinical properties, was assessed in a first patient. In line with its preclinical data, PET imaging resulted in clear visualization of the cancer lesions, with high contrast. Conclusion: The 64 Culabeled PSMA ligands are promising agents to target PSMA and visualize PSMA-positive tumor lesions as shown in preclinical evaluation by small-animal PET studies, organ distribution, and a patient application. Most importantly, the images obtained at 20 h enabled delineation of unclear lesions, showing that the compounds fulfill the prerequisite for dosimetry in the co...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

et al. 2019

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“…64 Cu ligands have logistical advantages for centers without 68 Ge/ 68 Ga generators, and with a half-life of 12.7 h 64 Cu can be easily transported from other production facilities [15]. Moreover, 64 Cu has a lower positron range than 68 Ga resulting in a better spatial resolution that could improve the detection of small lesions [14].…”

Section: Discussionmentioning

confidence: 99%

64Cu-DOTATOC PET-CT in Patients with Neuroendocrine Tumors

et al. 2019

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Introduction: Several radiolabeled somatostatin analogues have been developed for molecular imaging of neuroendocrine tumors (NETs) with single-photon emission computed tomography (SPECT) and positron-emission tomography (PET). The aim of the present study was to report our first results using 64 Cu-DOTATOC in patients with NETs. Methods: Thirty-three patients with NETs (15 female, 18 male; mean age 64 ± 13 years) were included in this retrospective study. 64 Cu-DOTATOC PET-CT scans were performed on all patients. Results: Five out of 33 patients with a history of NET after surgical removal of the primary lesion showed no pathological lesions on PET-CT imaging and 8/33 patients had enhanced uptake in the area of recurrent meningioma at the skull base. The remaining 20/33 patients had a history of neuroendocrine tumor in the gastrointestinal tract (GEP-NET) and were presented with at least one pathological lesion. Conclusion: The high detection rate of suspected lesions in patients with NETs and the high target-to-background contrast found in this study hold promise for the safe application of 64 Cu-DOTATOC in patients with NET.

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“…Compared to DOTA and TETA, additional cyclen and cyclam derivatives revealed improved stability in vivo (for an overview, see [75]). Recently, 1,4,7-triazacyclononane-N,N',N"-triacetic acid (NOTA) derivatives were investigated for the complexation of copper-64 and in several studies, this chelating system demonstrated good performance with high labelling yields and improved stability in vivo [76][77][78].…”

Section: Coppermentioning

confidence: 99%

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Rangger

Haubner

2020

Pharmaceuticals

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This review deals with the development of peptide-based radiopharmaceuticals for the use with positron emission tomography and peptide receptor radiotherapy. It discusses the pros and cons of this class of radiopharmaceuticals as well as the different labelling strategies, and summarises approaches to optimise metabolic stability. Additionally, it presents different target structures and addresses corresponding tracers, which are already used in clinical routine or are being investigated in clinical trials.

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Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer

Abstract: Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.

Cited by 16 publications

References 14 publications

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

64Cu-DOTATOC PET-CT in Patients with Neuroendocrine Tumors

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

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