Flare on Serial PSMA-Targeted ¹⁸F-DCFPyL PET/CT Examinations in Castration-Resistant Prostate Cancer: First Observations

Abstract

A 71-year-old man with castration-resistant prostate cancer (CRPC) demonstrated a flare phenomenon on ^99mTc-MDP and CT after 10 weeks of enzalutamide. Prostate-specific membrane antigen (PSMA)-targeted ¹⁸F-DCFPyL PET/CT demonstrated minimal uptake at sites of baseline bone and lymph node disease with increasing uptake at sites of osseous disease following therapy. While this is likely related in part to decreased androgen receptor activity and a consequent increase in PSMA expression, other mechanisms (neovascularization, cell infiltration from the bone repair process, osteoblastic turnover, or minimal radiotracer impurity) may also be involved in causing the increased ¹⁸F-DCFPyL uptake at sites of osseous flare.

Figure 1.

(A) ^99mTc-MDP skeletal scintigraphy and diagnostic CT performed at baseline, (B) after 10 weeks, and (C) after 6 months of enzalutamide in a 71-year-old man with known CRPC, who had previously been naïve to treatment with a second generation anti-androgen. Osseous disease at baseline became more sclerotic/conspicuous on the follow-up bone scan and CT after 10 weeks of therapy (white arrows) correlating with decreasing PSA (D). The 6 month follow-up bone scan and CT confirms a flare phenomenon, similar to that described in the literature^1–4. There was also lymph node disease on the baseline diagnostic CT (pink arrows) that improved on the diagnostic CT scans obtained after 10 weeks and 6 months of therapy. PSA nadir was seen at approximately 6 months post-initiation of enzalutamide, and therapy was discontinued at 1 year due to progression.

Figure 2.

(A) PSMA-targeted ¹⁸F-DCFPyL PET/CT at baseline and (B) after 10 weeks of enzalutamide in the same man. At baseline, there was minimal to no significant radiotracer uptake at the sites of bone and lymph node disease seen on the bone scan and diagnostic CT. After 10 weeks of therapy there was significant increase in radiotracer uptake correlating with increased sclerosis in L2 (white arrows). ¹⁸F-DCFPyL is known to have high uptake at sites of metastatic prostate cancer^5,6; however, this case shows limited ¹⁸F-DCFPyL uptake at sites of disease, underscoring the fact that PSMA expression in prostate cancer cells is variable^7,8 and uptake of PSMA-targeted agents may reflect this variability.

Figure 3.

(A) ¹⁸F-DCFPyL PET/CT at baseline and (B) after 10 weeks of therapy in the same man show mild increased radiotracer uptake correlating with increased sclerosis in a small site of disease in the right iliac bone adjacent to the sacroiliac joint.

Figure 4.

(A) ¹⁸F-DCFPyL PET/CT at baseline and (B) after 10 weeks of therapy in the same man show mildly avid predominantly lytic disease in the right iliac bone anteriorly at baseline that decreased slightly following therapy. This site of disease showed minimal increased sclerosis following therapy.

Figure 5.

(A) ¹⁸F-DCFPyL PET/CT at baseline and (B) after 10 weeks of therapy in the same man showed no significant radiotracer uptake associated with lymph nodes seen on CT either at baseline or following therapy (pink arrows). Although it has been suggested that exposure to androgen deprivation therapy can increase PSMA expression and radiotracer uptake on PSMA targeted PET/CT, this was not seen here at sites of lymph node disease. Also, literature shows PET detects up-regulation of PSMA in response to androgen deprivation therapy^9,10; however the only sites of increasing radiotracer uptake were at sites of osseous flare. Since ¹⁸F-DCFPyL uptake can occur at sites of benign osseous disease such as Paget disease¹¹ or metastatic prostate cancer to bone with a predominantly osteoblastic reaction and few viable tumor cells¹², in addition to changes in androgen receptor signaling, possible hypotheses for uptake at sites of osseous flare include: neovascularization, cell infiltration from bone repair, or osteoblastic turnover.