Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density

Abstract

Purpose Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82 Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na + /K +-ATPase density, which is relevant as 82 Rb is transported intracellularly via the Na + /K +-ATPase. Methods One hundred and two patients were included for pelvic 82 Rb PET scan prior to magnetic resonance imaging (MRI)guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82 Rb PET for TBF measurement. Immunohistochemical Na + /K +-ATPase staining was subsequently performed on biopsies. Results TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = −0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na + /K +-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na + /K +-ATPase density determined tumour 82 Rb uptake. Conclusion TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness

“…The coherency between quantitative TBF and PCa aggressiveness is being established, and the present results are in line with our previous publications [31,33]. However, the potential clinical role of quantitative TBF is undetermined in PCa management.…”

“…Across our previous studies [31][32][33], 43 patients underwent both pelvic [ 82 Rb]Rb PET/CT and clinical [ 68 Ga] Ga-PSMA-11 PET/CT and thereby met the inclusion criteria for the present study. All patients were recruited at the time of primary staging and hence none had previous therapy.…”

“…In a recent large clinical study, we consolidated the positive correlation between TBF and PCa aggressiveness and found [ 82 Rb] Rb TBF superior to apparent diffusion coefficient (ADC) from multiparametric (mp) magnetic resonance imaging (MRI) in differentiating between clinically significant and insignificant PCa [33]. Inflammatory lesions displayed increased [ 82 Rb]Rb TBF [33].…”

Recent Advances in Cardiovascular Diseases Research Using Animal Models and PET Radioisotope Tracers

“…Application of 82 Rb as a Sodium-Potassium ATPase Pump Marker Rubidium-82 ( 82 Rb) has a similar biological pathway to that of a potassium ion (K + ). Once in the myocardium, it is taken up as a potassium analogue in the ion exchange pump (Na + /K + ATPase-pump) in cells [151]. Then, it is extracted proportional to blood flow: radioactivity is increased in viable myocardial cells, while the tracer is cleared rapidly from necrotic or infarcted tissue.…”

Non-invasive radionuclide imaging of trace metal trafficking in health and disease: “PET metallomics”

“…Jochumsen et al demonstrated increased uptake in higher grade prostate cancer compared to lower grade. 19 Like all blood-borne radiotracers, the tissue accumulation is governed both by perfusion and the abundance of the specific molecular target or binding mechanism. Which of these contributors dominates, and hence whether or not 82 Rb imaging can quantify Na + /K + -ATPase activity (either in cardiac or tumour imaging), remains to be fully determined.…”