Combined Intravenous Urogram and 68Ga-PSMA PET/ CT for Improved Staging and Restaging of Prostate Cancer
Staging and restaging of prostate cancer is critical in determining prognosis and strategies for disease management. Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained prominence for prostate cancer staging at Australian centers, as well as internationally. 68Ga-PSMA PET/CT has shown high sensitivity and specificity for prostate cancer recurrence in several studies. However, at this time, no high-level evidence from randomized control trials is available. This situation, where adoption in clinical practice has outstripped the availability of high-level evidence, means each center offering 68Ga-PSMA PET/CT will have a protocol based on their own experiences.
At our center, 68Ga-PSMA PET/CT was introduced in June 2014. In April 2017, we updated our protocol to include a modified intravenous urogram. This method quickly became our standard practice, based on radiologist consensus that it enabled improved discrimination between radiotracer activity in the renal tract, normal variants, physiological uptake, and small pelvic nodes or local recurrences.
Our protocol commences with the administration of an intravenous (IV) bolus of 150–250 MBq 68Ga-PSMA-11 ligand complex (1.8–2.2 MBq per kilogram of body weight) and an uptake period ranging from 45 to 60 min. Administration of 25 mL of IV contrast occurs 10 min before imaging acquisition. A low-dose CT (120 KeV and 10–30 mAs) is performed first, from the calvarial vertex to proximal thighs with the patient lying supine. Concurrent PET imaging is performed of the same region, commencing proximal thighs to calvarial vertex with 8–11 bed frames (depending on the length of the patient), with an acquisition time of 3 min/bed (4 min/bed over pelvis). Finally, a second dose of 75 mL of IV contrast is administrated for the IVU and diagnostic CT, incorporating the pelvis, abdomen, chest, neck, and head. PET/CT systems are used for sequential low-dose CT, PET, and diagnostic CT image acquisition (Phillips Ingenuity TF 128 slice PET/CT, Phillips Healthcare, Amsterdam, Netherlands or GE Discovery MI DR PET/CT, GE Healthcare, Chicago, USA). Reconstructions on PET/CT emissions data are applied for attenuation correction, to minimize scatter and decay, reconstructions are also applied to diagnostic CT data. Further processing is done on appropriate workstations to create fusion images, MIPs, and plane reconstructions.
This protocol shows the contrast in the pelvic ureters and bladder 3 times over the imaging course, thus enabling a detailed assessment of high-risk structures, including both ureters with peristalsis, small nodes, and the bladder base. In early images, a small amount of contrast is seen in the pelvicalyceal systems and ureters. In mid images, contrast is seen in the pelvic arteries, the distal third of the ureters, and the bladder. In late images, contrast is seen in the aorta, inferior vena cava, pelvic arteries and veins, pelvicalyceal systems, ureters, and bladder. Ultimately, this combined method allows for differentiation based on contrast opacification and PSMA uptake. For example, a malignant node adjacent to the ureter [Figure 1] or bladder [Figure 2] will show PSMA uptake and no contrast opacification, compared to the adjacent structures which will show both PSMA uptake and contrast opacification. Similarly, tumor recurrence at a surgical site, either from previous TURP [Figure 3] or prostatectomy [Figure 4], can be differentiated from surgical changes as the tumor will show PSMA uptake and no contrast opacification. Similarly, in Figure 5, PSMA uptake observed at a suspected site of tumor recurrence was difficult to differentiate from the adjacent non-dilated ureter. In this scenario, IVU imaging allows tracing of contrast opacification down the ureters, aiding in differentiation. Further, this imaging approach is of utility in assessing prospective radioligand therapy patients, as in addition to disease restaging, kidney function is also demonstrated [Figure 6].
Normal variants, physiological uptake, and excretion of 68GaPSMA through the renal system present significant challenges in the assessment of 68Ga-PSMA PET/CT examinations. This challenge is clinically important as pelvic lymph nodes and the bladder base are common sites of metastasis. Other authors have proposed alternative methods for this problem. These include the administration of furosemide concurrently with 68Ga-PSMA;[3,4] furosemide 60 min post-injection followed by delayed imaging at 180 min; and early pelvic images to avoid tracer accumulation. At our center, we do not utilize furosemide as this requires close attention to the patient’s hydration status and can be limited by comorbidities that contraindicate the use of diuretics. Further, methods which incorporate large delays and multiple time-points are impractical in high-throughput centers, and those which incorporate early pelvic images can result in false negatives given low lesional uptake. Of note, a similar protocol to ours, combining 68Ga-PSMA PET/CT and IVU, but without the diagnostic quality CT, have been reported by Iravani et al., who retrospectively determined this approach assisted in the interpretation of 17.5% of cases. We believe that our imaging protocol is likely to improve the interpretation of a similar, if not higher, number of cases as our urogram protocol contains more phases, with the added advantage of also being able to detect other pathologies on the diagnostic CT component, as reported by McEwan et al. In this retrospective review of 1200 prostate cancer scans at our center, significant pathologies, often of greater clinical importance than the patient’s prostate cancer, were identified in 5.7% of examinations due to the parallel interpretation of PET and diagnostic quality CT images.
There is no consensus regarding the optimal protocol for 68Ga-PSMA PET/CT. Our method was implemented as an in-house solution to the difficulties posed by renal excretion of 68Ga-PSMA and we do not have prospective data comparing our method with alternative imaging approaches. Within this pictorial essay, we present multiple examples of cases which would have presented significant interpretation difficulties if a combined protocol had not been utilized.