Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted ¹⁸F-DCFPyL PET/CT

Abstract

Objective: Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, ¹⁸F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose.

Methods: Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer ¹⁸F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. ¹⁸F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease.

Results: In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal ¹⁸F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. ¹⁸F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6-19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for ¹⁸F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9%).

Conclusions: PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as ¹⁸F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature.

Keywords: DCFPyL; Positron emission tomography (PET); Prostate-specific membrane antigen (PSMA); Renal cell carcinoma (RCC).

Fig. 1

MIP image of patient #2 who was status post-right nephrec-tomy with multiple sites of metastatic disease. Normal radiotracer uptake is noted in the lacrimal glands, salivary glands, oropharynx, nasopharynx, liver, spleen, proximal small bowel, left kidney, left ureter, and bladder. Abnormal sites of uptake include a brain lesion (red arrowhead), lung nodules as well as mediastinal and hilar lymph nodes (red bracket), a retroperitoneal lymph node (thick red arrow), and a soft tissue perineal lesion (thin red arrow) (color figure online)

Fig. 2

4-mm intensely radiotracer-avid anterior mediastinal lymph node (SUV_max 19.3) from patient #2, as demonstrated on contrast-enhanced CT (a) and ¹⁸F-DCFPyL PET/CT (b) (arrowheads)

Fig. 3

T3 vertebral body bone lesion from patient #5 which was occult on contrast-enhanced CT of the chest (a), but demonstrated moderate radiotracer uptake (SUV_max 2.6) when imaged with ¹⁸F-DCFPyL PET/CT (b) (arrowheads)

Fig. 4

Metastatic lesions to the pancreatic tail in patient #1 (SUV_max 5.0 in the more anterior lesion and SUV_max 7.4 in the more posterior lesion) as noted on contrast-enhanced CT (a) and ¹⁸F-DCFPyL PET/CT (b) (arrowheads)

Fig. 5

Subtle radiotracer uptake (SUV_max 1.7) in a small lung nodule (1 cm in diameter) as seen on contrast-enhanced CT (a) and ¹⁸F-DCFPyL PET/CT (b) (arrowheads) in patient #2

Fig. 6

Axial contrast-enhanced T1-weighted MRI of the brain (a) and ¹⁸F-DCFPyL PET/CT (b) from patient #2 demonstrating an intensely ¹⁸F-DCFPyL-avid (SUV_max 3.9) brain lesion in the left frontal lobe (arrowheads)