Prospective Evaluation of ⁶⁸Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging

Abstract

Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a Tc-methylene diphosphonate bone scan) before enrollment. The observedGa-RM2 PET detection rate was 71.8%. Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings ( = 0.006). Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests thatGa-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging.

The Effect of Including Bone in Dixon-Based Attenuation Correction for 18F-Fluciclovine PET/MRI of Prostate Cancer

“…(4,18,22,23), and detection of disease recurrence after initial treatment with curative intent, e.g. (24)(25)(26)(27). However, in current clinical practice, the high linear attenuation coefficients of the bones in the pelvis and lower abdomen are assumed to be equal to those of soft tissue, which is incorrect.…”

68Ga-Radiopharmaka: Methode oder Episode?

“…Markierungschemie 18 F ist ein kleines Atom, welches sich auch in kleine Moleküle einfügen lässt, ohne große Veränderungen der chemischen Struktur und biologischen Wirkung hervorzurufen. 18 F ist preiswert Über die 18 O(p,n) 19 Im Vergleich dazu besitzt 68 Ga nachteilige Nuklideigenschaften: Die Halbwertszeit ist deutlich kürzer (t ½ = 68 min), der Anteil an Positronenzerfall ist geringer (89 %) und die höhere Positronenenergie (E av,β+ = 862 keV, E max,β+ = 1899 keV) bewirkt eine etwas schlechtere räumliche Auflösung, weil die Positronen das Gewebe besser durchdringen. 68 Ga besitzt allerdings auch klare Vorteile.…”

“…Ein weiterer Antagonist, 68 Ga-RM2, zeigte vielversprechende Ergebnisse bei Patienten mit primärem Prostatakrebs, wobei Lymphknoten-und v. a. Knochenmetastasen mit geringerer Sensitivität dargestellt wurden. In einer prospektiven Studie an Patienten mit BCR von PCa und negativer konventioneller Bildgebung [19] wurden mit 68 Ga-RM2-PET in 23 von 32 Fällen mit bio-chemischem Rezidiv eine hohe fokale Aufnahme beobachtet. Der direkte Vergleich von 68 Ga-RM2 und 68 Ga-PSMA-11 in 7 Patienten mit metastasiertem PCa zeigte nicht nur eine unterschiedliche physiologische Anreicherung der Tracer (PSMA: Speicheldrüsen, Nieren > > Abdomen; GRPR: Pankreas), sondern belegte auch, dass GRPR-gerichtete Radiopharmaka ein hohes Potenzial für die Diagnostik (und vielleicht auch Therapie) von Prostatakarzinomen besitzen.…”

Comparison of biological properties of [177Lu]Lu‐ProBOMB1 and [177Lu]Lu‐NeoBOMB1 for GRPR targeting

“…[1][2][3][4][5] BBN, a peptide isolated from the frog, Bombina bombina, has a mammalian ortholog named the gastrin-releasing peptide (GRP) and both bind GRPR. 7,[9][10][11][12] 13,14 In a previous article, we modified a sequence initially published by the Schally group, RC-3950-II, to adapt it for theranostic application yielding DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-ψ-Pro-NH 2 (ProBOMB1), which we characterized after labeling with nat/68 Ga. 8,15 The radiotracer, [ 68 Ga]Ga-ProBOMB1, had excellent characteristics for imaging GRPR. In nuclear medicine, the use of peptides as delivery vectors is an effective strategy for targeting GPCRs (ie, somatostatin, CXC chemokine receptor 4, cholecystokinin-2, and substance P).…”

“…In particular, some BBN derivatives have been shown effective as theranostic agents when coupled with diagnostic and therapeutic radiometals in a preclinical setting and as diagnostic agents in patients. 7,[9][10][11][12] Examples of agents tested in the clinic include [ 68 Ga]Ga-NeoBOMB1, [ 68 Ga]Ga-RM2, [ 68 Ga]Ga-SB3, [ 64 Cu]Cu-CB-TE2A-AR06, [ 68 Ga]Ga-NOTA-Aca-BBN, and [ 99m Tc]Tc-demobesin-4. 13,14 In a previous article, we modified a sequence initially published by the Schally group, RC-3950-II, to adapt it for theranostic application yielding DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-ψ-Pro-NH 2 (ProBOMB1), which we characterized after labeling with nat/68 Ga. 8,15 The radiotracer, [ 68 Ga]Ga-ProBOMB1, had excellent characteristics for imaging GRPR.…”