Synopsis

In this feasibility study, hyperpolarized ¹³C-pyruvate MR exams were conducted on 5 patients who had metastatic prostate cancer to bone or liver. In one man with liver metastasis, serial scans showed a decrease of pyruvate-to-lactate conversion k_PL (0.026 to 0.015 s^-1) at 2 months after initiation of chemotherapy that was consistent with response based on PSA and RECIST criteria. High k_PL was found in patients with bone lesions comparable to that in high-grade primary prostate cancer. Overall, HP-¹³C MR imaging showed great promise as a biomarker to evaluating treatment responses in metastatic prostate cancer.

Purpose

Methods

Sequences: The HP-¹³C images were acquired using a 2D dynamic MRSI sequence with a slice-selective spectral-spatial excitation, followed by phase-encode and echo-planar spectroscopic imaging readout⁵. Some sequence parameter are as follows, TR/TE = 130ms/3.5ms, 3s temporal resolution, constant flip angle Pyr 10°, Lac 20°. LAVA and SSFSE series were acquired as references.

Patient Studies: A cohort of 5 patients with metastatic prostate cancer were examined in this study, targeting either pelvic or chest bone lesions on 4 of them. One patient with liver metastasis was scanned prior to and 2-month after initiation of chemotherapy. GMP [1-¹³C] pyruvic acid was polarized in a 5T SPINLab polarizer for 2-3 hours, and dissolutions yielded 235±10 mM sterile pyruvate with 37.4±3.5% polarization, 0.6±0.4μM radical and 30.9±0.5°C temperature. A ¹³C transmit-receive surface coil targets the bone and liver lesions, and proton imaging was conducted using a 16-channel receiver array (Fig.1B). All studies were approved by IRB at UCSF.

Data Processing: The 2D dynamic MRSI datasets were processed by applying even-odd lobe phasing, B₀-shift correction, tensor-low-rank denoising⁶, baseline correction, followed by a phase-sensitive peak quantification. The pyruvate-to-lactate conversion k_PL was evaluated using an inputless single-compartment two-site exchange model⁷.

Results and Discussions

The patient cohort is summarized in the table in Figure.1A. Figure.2 showed a 75 y/o patient with mCRPC who had several large osteoblastic lesions throughout the left hemipelvis and involving left femur. CT identified a relatively osteolytic lesion in left ilium. Regions of high pyruvate-to-lactate conversion rate (k_PL) correlated with the osseous lesion on both CT and MR (Fig.2A,B). k_PL was calculated 0.013(s^-1) at the targeted lesion, where Fig.2C,D showed the spectra over time and the inputless two-site kinetic fit, respectively.

Figure.3 illustrated a 57 y/o individual with mCRPC to the liver. Chemotherapy of carboplatin+docetaxel started ~1 month post- baseline scan. Follow-up 2 months after initiation of therapy found interval decrease of lesion size (19.3mm to 11.8mm) that indicated response based on RECIST criteria (Fig.3A), accompanied by PSA decrease (25 to 13.4 ng/ml). Between the baseline and follow-up HP-¹³C exam, interval decrease of pyruvate-to-lactate conversion rate k_PL was observed from 0.026(s^-1) to 0.015(s^-1) that correlated to response (Fig.3B). Partial volumes increase as tumor shrinks, meaning the actual k_PL decrease could be more prominent than measured. Note the portal venous bolus around 50-60s post-injection. The lactate there could be largely vascular, coming from intestines.

Figure.4 showed an 83 y/o patient with osteoblastic metastatic disease throughout rib cage, spine and pelvis. CT and LAVA images identified osseous lesions on right anterior 4 and 5th rib, measuring 5.1x4.0cm, with soft tissue components (Fig.4A). In vivo biodistribution of HP-¹³C biomarkers was illustrated by pyruvate and lactate signals maps summed over time (Fig.4B). k_PL of 0.017(s^-1) was found in the targeted lesion. Coincidentally, this k_PL value was comparable to those observed in aggressive primary prostate adenocarcinoma of a patient cohort prior to radical prostatectomy⁸.

Figure.5 showed a 72 y/o man who had extensive disease in rib cage, spine and pelvis. CT identified an osteoblastic lesion at right iliac crest (Fig.5A) As illustrated in Fig.5C, k_PL at the iliac crest lesion was calculated 0.026(s^-1).

In summary, k_PL decrease was found on one patient indicating response to chemotherapy, which agreed with PSA and RECIST criteria. On patients with bone metastases, high k_PL values were observed comparable to aggressive primary prostate cancer.

Conclusions

Acknowledgements

References

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