[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center

Abstract

Background: Prostate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [^99mTc]Tc-PSMA-I&S is a new ^99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [^99mTc]Tc-PSMA-I&S-SPECT/CT in PCa.

Results: [^99mTc]Tc-PSMA-I&S-SPECT/CT was performed and evaluated in 210 outpatients with PCa at a single center. Patients were imaged for biochemical recurrence (BCR, n = 152, mean PSA 8.7 ng/ml), for primary staging of high-risk PCa (n = 12, mean PSA 393 ng/ml), and restaging in advanced recurrent PCa (n = 46, mean PSA 101.3 ng/ml). Number and location of positive lesions were determined for the different subgroups. For BCR, detection rates were calculated, defined as the proportion of scans with at least one PSMA-positive lesion. PSMA positive lesions were detected in 65.2% of all 210 patients. Tumor tissue was mainly detected in lymph nodes (59%), in the bone (42%), and in the prostate (fossa) (28%). In the subgroup of patients referred for detection of BCR the detection rate increased from 20% at a PSA level < 1 ng/ml to 82.9% and 100% at PSA levels > 4 ng/ml and > 10 ng/ml, respectively. In the subgroup of high-risk patients referred for primary staging, 42% demonstrated metastatic disease. Restaging of advanced recurrent PCa revealed detectability of PSMA positive tumor lesions in 85% of the scans.

Conclusions: [^99mTc]Tc-PSMA-I&S-SPECT/CT was useful in PSMA-targeted imaging of PCa at various clinical stages. At low PSA levels (< 4 ng/ml), detection rates of [^99mTc]Tc-PSMA-I&S-SPECT/CT in BCR are clearly inferior to data reported for PET-imaging and should thus only be considered for lesion detection if imaging with PET is unavailable. However, at higher PSA levels (> 4 ng/ml) [^99mTc]Tc-PSMA-I&S-SPECT/CT provides high detection rates in BCR. [^99mTc]Tc-PSMA-I&S-SPECT/CT can also be used for primary staging and for restaging of advanced recurrent PCa. However, further studies are needed to assess the clinical value in these indications.

Keywords: PSMA; Prostate cancer; SPECT; Scintigraphy; [99mTc]Tc-PSMA-I&S.

Fig. 1

SPECT/CT at 5 h post injection (p.i.) and pairs of ventral/dorsal planar images at 5 h and 20 h p.i. of [^99mTc]Tc-PSMA-I&S. a, b SPECT/CT suggested paraaortic lymph node metastases, but the planar scintigraphy (c, d) shows significant hepatobillary and gastrointestinal uptake and suggests urinary secretion. To further distinguish between tumor uptake in paraaortic lymph nodes and unspecific uptake in the ureter (red arrows), a late planar image was taken. e, f Planar scintigraphy at 20 h p.i. Paraaortic uptake remained high and was thus classified as lymph node metastases (red arrows). Note: there was a tracer accumulation in the primary tumor over time, resulting in a better contrast between unspecific bladder signal and the [^99mTc]Tc-PSMA-I&S uptake in the prostate (green arrows). Late imaging was restricted to a single bed planar scintigraphy because the low activity at 20 h p.i. would have led to inappropriately high examination times (~ 60 min for planar whole body scintigraphy and whole body SPECT/CT)

Fig. 2

Location of tumor tissue in 137 PSMA-positive scans

Fig. 3

Lesion detection in BCR and monitoring of radiation therapy in a 72-year-old patient with Gleason 7 PCa, who underwent primary surgery and salvage radiation therapy. a Cancer recurrence was detected in the right clavicle (PSA 3.8 ng/ml) which was followed by targeted radiation. b 6 months later the clavicle was unremarkable but another recurrence was detected in the lung (PSA 6.8 ng/ml) again followed by precision radiotherapy. c Another 6 months later, no tumor recurrence was detected (PSA 0.56 ng/ml). Note: the apparent focal PSMA-positivity in the liver (c) could not be confirmed in the cross-sectional planes and was not categorized as PSMA-positive

Fig. 4

[^99mTc]Tc-PSMA-I&S-SPECT/CT in primary high risk PCa. a 71-year-old man with Gleason 9 PCa (PSA 46 ng/ml). Apart from the primary tumor (green arrow), increased PSMA expression was detected in one lymph node in the right iliac region and in the left inguinal region (red arrows)(TxN1M0). b 77-year-old man with Gleason 9 PCa (PSA 80 ng/ml). PSMA expression was increased in the primary tumor only (green arrow), no metastases were detected (TxN0M0)

Fig. 5

[^99mTc]Tc-PSMA-I&S-SPECT/CT of an 82-year-old patient with mCRPC and disease progression under chemotherapy (docetaxel). a Pretherapeutic tumor spread (PSA 137 ng/ml). b Restaging 3 months after the second cycle of ¹⁷⁷Lu-PSMA therapy (PSA 60 ng/ml)

Fig. 6

[^99mTc]Tc-PSMA-I&S-SPECT/CT of a 71-year-old patient with mCRPC and disease progression and severe fatigue after the second cycle of chemotherapy (docetaxel). a Pretherapeutic tumor spread in paraaortic and pelvic lymph nodes (PSA 335 ng/ml). b Restaging 3 months after 2 cycles of ¹⁷⁷Lu-PSMA therapy (PSA 0.6 ng/ml). [^99mTc]Tc-PSMA-I&S-SPECT/CT was negative

Fig. 7

[^99mTc]Tc-PSMA-I&S-SPECT/CT of a 59-year-old patient with radical prostatovesiculectomy and salvage radiotherapy. According to morphological imaging 2 years later osseous metastases were suspected. a At baseline, multiple osseous and lymph node metastases (partly marked with red arrows) were detected with mostly mild PSMA expression (PSA 4.75 ng/ml). b Follow-up scan 4 months later under antihormonal therapy (PSA 0.01 ng/ml). [^99mTc]Tc-PSMA-I&S-SPECT/CT was negative

Fig. 8

Detection rates of different PSMA ligands in recurrent PCa. The figure was adapted from PSMA imaging detection rates from Su H-C. et al. [6] (Blue), Eiber M. et al. [10] (green), Schmidkonz C. et al. [4] (yellow), and the present study (red)