68Ga-PSMA-HBED-CC PET/CT imaging for adenoid cystic carcinoma and salivary duct carcinoma: a phase 2 imaging study

Theranostics. 2020 Jan 12;10(5):2273-2283. doi: 10.7150/thno.38501. eCollection 2020.

Abstract

Rationale: Treatment options for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC), major subtypes of salivary gland cancer, are limited. Both tumors often show overexpression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA-ligands labeled with 68Ga or 177Lu are used for imaging and therapy, respectively. Primary aim of this study in R/M ACC and SDC patients was to systematically investigate 68Ga-PSMA-uptake by PET/CT imaging to determine if PSMA radionuclide therapy could be a treatment option. Methods: In a prospective phase II study, PET/CT imaging was performed 1 h post injection of 68Ga-PSMA-HBED-CC in 15 ACC patients and 10 SDC patients. Maximum standardized uptake values (SUV) were determined in tumor lesions. Immunohistochemical PSMA expression was scored in primary tumors and metastatic tissue. Standard imaging (MRI or CT) was performed for comparison. Results: In ACC patients, SUVmax ranged from 1.1 to 30.2 with a tumor/liver-ratio >1 in 13 out of 14 evaluable patients (93%). In SDC patients, SUVmax ranged from 0.3 to 25.9 with a tumor/liver-ratio >1 in 4 out of 10 patients (40%). We found a large intra-patient inter-metastatic variation in uptake of 68Ga-PSMA, and immunohistochemistry did not predict ligand uptake in ACC and SDC. Finally, PSMA-PET detected additional bone metastases compared to CT in 2 ACC patients with unexplained pain. Conclusion: In 93% of ACC patients and 40% of SDC patients we detected relevant PSMA-ligand uptake, which warrants to study PSMA radionuclide therapy in these patients. Additionally, our data provide arguments for patient selection and treatment timing. Finally, PSMA-PET imaging has added diagnostic value compared to CT in selected patients.

Keywords: Adenoid cystic carcinoma; Immunohistochemistry; Positron-Emission Tomography; Prostate-specific membrane antigen; Salivary duct carcinoma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Surface / metabolism
  • Carcinoma, Adenoid Cystic / diagnostic imaging*
  • Carcinoma, Ductal / metabolism*
  • Carcinoma, Ductal / therapy
  • Edetic Acid / administration & dosage
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / pharmacokinetics
  • Edetic Acid / therapeutic use
  • Female
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neoplasm Metastasis / diagnostic imaging
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / pathology
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / therapeutic use
  • Positron Emission Tomography Computed Tomography / methods*
  • Prospective Studies
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Salivary Ducts / pathology
  • Salivary Gland Neoplasms / pathology

Substances

  • Antigens, Surface
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Oligopeptides
  • Radiopharmaceuticals
  • gallium 68 PSMA-11
  • N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid
  • Edetic Acid
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II