Differential Metabolism and Pharmacokinetics of l-[1-¹¹C]-Methionine and 2-[¹⁸F] Fluoro-2-deoxy-d-glucose (FDG) in Androgen Independent Prostate Cancer

Abstract

Metabolic imaging with positron emission tomography (PET) for the staging and monitoring of treatment response has important implications in clinical oncology. The choice of radiotracer is likely to be critically important. The objective of our study was to compare the pharmacokinetics of C-11-methionine with FDG in a group of androgen independent patients with metastatic prostate cancer, to determine the differential metabolism of the two tracers, and to determine the optimal time of imaging after injection in treated and untreated patients. A total of 29 dynamic scans (19 pretreatment and 10 posttreatment) were performed in 10 patients with progressive or new lesions on bone scans (index lesions). A total of 13 index lesions were identified in baseline scans. Patients were infused with 370 MBq C-11-methionine on the couch and 32 dynamic images acquired over 60 minutes. After at least 5 half-lives of C-11, patients were then dynamically imaged (15 frames) for 45 minutes with FDG. Index lesions demonstrated both C-11-methionine (13/13) and FDG uptake (12/13). The plateau of methionine uptake in tumor was reached by 10 minutes, and thereafter remained constant. FDG tumor uptake was slower and for some patients continued to rise beyond 45 minutes. The clearance of blood activity for C-11-methionine was more rapid than FDG and the plateau was 10 and 45 minutes respectively. In 5 patients scanned after therapy, 4 responded to treatment, which was reflected by a corresponding decrease in C-11-methionine and FDG tumor uptake. No change was observed in the relative shape of the uptake curves however, between the C-11-methionine and the FDG uptake, either in the 4 who responded to treatment or for one patient who did not respond. The SUV of C-11-methionine was significantly higher than for FDG (P < .008). Both C-11-methionine and FDG are taken up in index lesions in patients with progressive prostate cancer. The advantages of C-11-methionine over FDG are the higher tumor to blood ratio, the more rapid tumor uptake allowing earlier imaging, and a flatter plateau rendering lesion activity on whole body images more uniform and less susceptible to gradual change than FDG. This indicates the feasibility of whole body PET imaging with decay corrected C-11-methionine. Additional studies are planned to define optimal imaging times after different therapies in comparison to FDG and bone scans.

Introduction

When prostate cancer metastasizes, it typically spreads to bone, where conventional staging methods involve the use of bone scanning, CT or MRI to determine the extent and monitor the progress of disease. Positron Emission Tomography (PET) has the potential ability to monitor the altered biology of common human tumors including prostate cancer in vivo. 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG), a tracer of glucose metabolism, has been highly successful for imaging of a variety of tumors and for monitoring response to therapy.¹ In a recent trial of PET-FDG in androgen independent prostate cancer performed here at Memorial Sloan-Kettering Cancer Center (MSKCC) only about 18% of the patients bony lesions metabolized FDG sufficiently to be seen on PET scanning.² These patients were relatively stable clinically, and a number of these patients had responded to hormonal therapy. Subsequently, we noted in several patients who had progressive tumors while on therapy, with rapidly changing PSA, that FDG uptake was more prominent. Shreve et al.³ concluded, in a preliminary study, that FDG PET can help identify osseous and soft-tissue metastases of prostate cancer with a high positive predictive value, but is less sensitive than bone scintigraphy for the identification of osseous metastases. In a preliminary report from Nilsson et al.,⁴ 12 patients with androgen independent prostate cancer underwent L-[1-¹¹C]-methionine labeled PET imaging. Uptake of the C-11 methionine radiotracer was discovered in all known sites of bone and soft tissue lesions of patients visualized by standard bone scintigraphy or cross sectional imaging. This study was done because: (A) We thought that FDG PET alone was not a good metabolic marker, therefore we rigorously controlled for progression by requiring patients to be studied to have a rising PSA and a positive bone scan. (B) We also performed post therapy scans in the same patient making this a unique study to compare both FDG and methionine. (C) Dynamic scans were performed to determine the optimal imaging time of imaging methionine. The objective of this study is to compare the pharmacokinetics of methionine with FDG in metastatic prostate cancer, determine the optimal time of imaging, and to assess the relative benefits of C-11-methionine versus FDG in assessing androgen independent prostate cancer.