Here, we present a case of persistent osteodynia and a sharp increase in neuron-specific enolase, carcinoembryonic antigen, and tissue polypeptide-specific antigen in the serum after receiving regular androgen deprivation therapy (ADT) and anti-osteoporosis treatment, following the diagnosis of prostate adenocarcinoma with a Gleason score of 5 + 5 by pathology and bone metastases by radionuclide bone imaging 15 months prior. ¹⁸F-AIF-NOTA-octreotide positron emission tomography (PET)/CT and ¹⁸F-PSMA (prostate membrane-specific antigen)-1007 PET/CT imaging were performed. We found that the uptake of octreotide and PSMA was completely different in different parts of the lesions, and the distribution of PSMA was superior to that of octreotide in most lesions, except for a lesion in the right scapula. ¹⁸F-AIF-NOTA-octreotide PET/CT illustrated that octreotide distribution was significantly increased in the right scapula lesion, while ¹⁸F-PSMA-1007 PET/CT showed mild uptake. Subsequent bone biopsy confirmed partial neuroendocrine differentiation of prostate cancer. Hence, the combined ligand PET/CT patterns, octreotide plus PSMA, could provide a basis for the early diagnosis of partial endocrine differentiation of prostate cancer, especially for patients with long-term ADT.

A 62-year-old man with initial prostate adenocarcinoma and multiple systemic bone metastases presented to our clinic after 15 months of regular hormone therapy as well as anti-osteoporosis treatment because of an excruciating bone ache and an increase in neuroendocrine tumor markers. The patient underwent both ¹⁸F-AIF-NOTA-octreotide PET/CT and ¹⁸F-PSMA-1007 PET/CT scanning. Most tracer-associated lesions in bones and prostate have been identified with higher uptake patterns than liver octreotide uptake on ¹⁸F-AIF-NOTA-octreotide PET/CT imaging (part A of Figure), while PSMA-associated lesions in bones and prostate were observed with lower uptake in the context of hepatic high PSMA background (part B of Figure). In general, PET/CT imaging showed that the distributions of both octreotide (part C of Figure) and PSMA (part D of Figure) were mildly increased in the prostate and bone metastases. Nevertheless, 2 bone metastases deserved our reconsideration: 1 lesion in the right iliac bone and another in the right scapula. Specifically, the lesion in the right iliac bone featured only mild octreotide uptake (maximum standard uptake value [SUVmax] =2.62; part E of Figure), but it showed significantly high PSMA uptake (SUVmax =9.68; part F of Figure). Although PSMA expression is decreased and the detection efficiency of tumor cells in PSMA ligand imaging is impacted after long-term, ADT,^1,2 metastatic lesions with significant PSMA enrichment have a high probability of prostate cancer because PSMA tracer imaging is highly consistent with pathological results.³ However, octreotide distribution was significantly increased in 1 lesion of the right scapula (SUVmax =18.22; part G of Figure) compared with PSMA distribution on ¹⁸F-PSMA-1007 PET/CT (SUVmax =2.83; part H of Figure). Given that the patient presented with persistent osteodynia before the PET/CT examination accompanied by a sharp increase in markers of neuroendocrine differentiation, including neuron-specific enolase, carcinoembryonic antigen, and tissue polypeptide-specific antigen, with the highest Gleason score (5 + 5), which is the only independent risk factor mediating endocrine differentiation of prostate adenocarcinoma,⁴ a bone biopsy was subsequently performed. The results of hematoxylin-eosin staining (part I of Figure) and immunohistochemistry (parts J and K of Figure) confirmed the partial neuroendocrine differentiation of prostate cancer based on the primary diagnosis (part L of Figure). Neuroendocrine differentiation of prostate adenocarcinoma is a dynamic process, and approximately 15%-20% of castration-resistant prostate cancers ultimately undergo neuroendocrine differentiation.^5,6 Because of the lack of effective early diagnosis, neuroendocrine prostate cancer often has a poor prognosis. The dynamic changes in PSMA and somatostatin receptor detected by whole-body ¹⁸F-PSMA-1007 PET/CT and ¹⁸F-AIF-NOTA-octreotide PET/CT may be able to manifest the process of neuroendocrine differentiation of prostate cancer. This case highlights that the dual-tracer uptake pattern with ¹⁸F-AIF-NOTA-octreotide and ¹⁸F-PSMA-1007 PET/CT explored the biological characteristics of prostate cancer cells from the expression of both somatostatin receptor and PSMA, not only effectively detecting the systemic tumor burden and precisely judging the disease stage, but also reflecting the dynamic process of neuroendocrine differentiation of prostate cancer.