Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer

Steve Y Cho, Kenneth L Gage, Ronnie C Mease, Srinivasan Senthamizhchelvan, Daniel P Holt, Akimosa Jeffrey-Kwanisai, Christopher J Endres, Robert F Dannals, George Sgouros, Martin Lodge, Mario A Eisenberger, Ronald Rodriguez, Michael A Carducci, Camilo Rojas, Barbara S Slusher, Alan P Kozikowski, Martin G Pomper, Steve Y Cho, Kenneth L Gage, Ronnie C Mease, Srinivasan Senthamizhchelvan, Daniel P Holt, Akimosa Jeffrey-Kwanisai, Christopher J Endres, Robert F Dannals, George Sgouros, Martin Lodge, Mario A Eisenberger, Ronald Rodriguez, Michael A Carducci, Camilo Rojas, Barbara S Slusher, Alan P Kozikowski, Martin G Pomper

Abstract

Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of (18)F-DCFBC in men with metastatic PCa.

Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of (18)F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1.

Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radioactivity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD).

Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of (18)F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for (18)F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as (18)F-FDG.

Figures

FIGURE 1
FIGURE 1
Mean biodistribution curves plotted for decay-corrected percentage injected dose per gram of organ mass vs. time. Time axis represents average time over all patients for each PET scan because some patients (i.e., tall patients) required more bed positions. (A) Organs with higher uptake. (B) Organs with lower uptake. (C) Increasing urinary bladder activity. LLI = lower large intestine; SI = small intestine; ULI = upper large intestine. %ID/g = percentage injected dose per gram of organ mass.
FIGURE 2
FIGURE 2
18F-DCFBC PET anterior projection maximal-intensity-projection images at 2 h after injection in patient 1, with several bone metastases (arrow) (A), and patient 5, with LN metastases (arrow) (B), as confirmed by correlation to CT portion of PET/CT exam.
FIGURE 3
FIGURE 3
Examples of concordant findings on 18F-DCFBC PET and CIM: (A) T12 bone metastasis (arrows) seen on bone scan (far right) and (B) retroperitoneal right external iliac LN (arrow) seen on CT (arrow).
FIGURE 4
FIGURE 4
(A and B) Focal 18F-DCFBC PET uptake at aortic bifurcation (arrow, A) with correlative small LN seen on concurrent contrast-enhanced CT (arrow, B), not considered to be nodal metastasis by CT but positive by PET. (C) Retrospective review of prior contrast-enhanced CT scan obtained 1 y previously demonstrates LN in this region (arrow).
FIGURE 5
FIGURE 5
Focal 18F-DCFBC PET uptake in L4 vertebral body on PET and fused PET/CT (thick arrows, A) with no correlative abnormality on CT (thin arrow, A) or bone scan (arrow, B).
FIGURE 6
FIGURE 6
(A) New sclerotic lesion in right posterior iliac bone seen on CT (thin white arrow) but not on 18F-DCFBC PET (black arrow) or PET/CT (thick white arrow). (B) Corresponding asymmetric uptake on bone scan (arrow).

Source: PubMed

3
구독하다