Dataset Information

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

ABSTRACT: The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal.

Methods

First, we prospectively performed neurotensin receptor-1 (NTS₁) IHC in a series of patients receiving both [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS₁ expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS₂, SST₂ and CXCR4.

Results

In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS₁ staining. No samples were negative for all three stains-for PSMA, GRP-R or NTS₁. In the autoradiography study, binding of [¹¹¹In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [¹¹¹In]In-PSMA-617 (9%). In these cases, binding of [¹¹¹n]In-JMV 6659 and [¹¹¹In]In-JMV 7488 towards NTS₁ and NTS₂ was high.

Conclusions

Targeting PSMA and NTS₁/NTS₂ could allow for the detection of all intraprostatic lesions.

SUBMITTER: Schollhammer R

PROVIDER: S-EPMC10137308 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

Schollhammer Romain R Quintyn Ranty Marie-Laure ML de Clermont Gallerande Henri H Cavelier Florine F Valverde Ibai E IE Vimont Delphine D Hindié Elif E Morgat Clément C

Cancers 20230418 8

The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal.<h4>Methods</h4>First, we prospectively performed neurotensin receptor-1 (NTS<sub>1</sub>) IHC in a series of patients receiving both [<sup>68</sup>Ga]Ga-PSMA-617 and [<sup>68</sup>Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n ...[more]

PMID: 37190273

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Project description:In the treatment of cancer, understanding the disease status, or accurate staging, is extremely important, and various imaging techniques are used. Computed tomography (CT), magnetic resonance imaging, and scintigrams are commonly used for solid tumors, and advances in these technologies have improved the accuracy of diagnosis. In the clinical practice of prostate cancer, CT and bone scans have been considered especially important for detecting metastases. Nowadays, CT and bone scans are called conventional methods because positron emission tomography (PET), especially prostate-specific membrane antigen (PSMA)/PET, is extremely sensitive in detecting metastases. Advances in functional imaging, such as PET, are advancing the diagnosis of cancer by allowing information to be added to the morphological diagnosis. Furthermore, PSMA is known to be upregulated depending on the malignancy of the prostate cancer grade and resistance to therapy. Therefore, it is often highly expressed in castration-resistant prostate cancer (CRPC) with poor prognosis, and its therapeutic application has been attempted for around two decades. PSMA theranostics refers to a type of cancer treatment that combines both diagnosis and therapy using a PSMA. The theranostic approach uses a radioactive substance attached to a molecule that targets PSMA protein on cancer cells. This molecule is injected into the patient's bloodstream and can be used for both imaging the cancer cells with a PET scan (PSMA PET imaging) and delivering radiation directly to the cancer cells (PSMA-targeted radioligand therapy), with the aim of minimizing damage to healthy tissue. Recently, in an international phase III trial, the impact of 177Lu-PSMA-617 therapy was studied in patients with advanced PSMA-positive metastatic CRPC who had previously been treated with specific inhibitors and regimens. The trial revealed that 177Lu-PSMA-617 significantly extended both progression-free survival and overall survival compared to standard care alone. Although there was a higher incidence of grade 3 or above adverse events with 177Lu-PSMA-617, it did not negatively impact the patients' quality of life. PSMA theranostics is currently being studied and used primarily for the treatment of prostate cancer, but it has the potential to be applied to other types of cancers as well.

Project description:BackgroundLutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.Materials and methodsAll patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [177Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20 mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion.ResultsIn 75 patients screened for Lutetium-177 [177Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm3 to 186 cm3 (median GTV volume = 4.3 cm3, IQR = 2.2 cm3 - 7.4 cm3). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 - 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20 mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5 mm from the GTV were bone/lung GTVs).ConclusionsCombined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

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Dataset Information

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

Methods

Results

Conclusions

Publications

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

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