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(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

ABSTRACT: Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities.(89)Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). (89)Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized.(89)Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls.This study demonstrated SSTr2-targeting specificity along with direct chelator-free (89)Zr-labeling of LPs and dual PET/MR imaging properties.

SUBMITTER: Abou DS

PROVIDER: S-EPMC3578092 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

Abou Diane S DS Thorek Daniel L J DL Ramos Nicholas N NN Pinkse Martijn W H MW Wolterbeek Hubert T HT Carlin Sean D SD Beattie Bradley J BJ Lewis Jason S JS

Pharmaceutical research 20121207 3

<h4>Purpose</h4>Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities.<h4>Methods</h4>(89)Zr oxophilicit ...[more]

PMID: 23224977

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Project description:PurposeWe present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands.ProceduresThe precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [177Lu]Lu-PSMA-617. The ligand [89Zr]Zr-PSMA-DFO was compared with [68Ga]Ga-PSMA-11 and [18F]F-JK-PSMA-7 in vitro by determination of the Kd value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [89Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [18F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously.Results[89Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very high in vitro stability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [89Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [68Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [18F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [89Zr]Zr-PSMA-DFO is comparable to [68Ga]Ga-PSMA-11 or [18F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [89Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUVmax 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides.Conclusion[89Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation.

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(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

Publications

(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

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