The efficacy of three therapeutic programs for acute leukemia were compared. These programs included (1) Methotrexate (Phase I) followed by 6-mercaptopurine (Phase II); (2) 6-mercaptopurine (Phase I) followed by Methotrexate (Phase II); and (3) Combination Therapy, i.e., 6-mercaptopurine given in combination with Methotrexate. In children with acute lymphocytic leukemia the remission rate was 59 per cent for combination therapy, 47 per cent for 6-mercaptopurine, and 29 per cent for Methotrexate. The better remission rate for combination therapy is consistent with that predicted if it is assumed that 6-mercaptopurine and Methotrexate act independently. The median duration of complete remissions for the three treatments was not different (4 to 5 months). However, long lasting remissions were more frequent in patients receiving combination therapy. The median survival from the onset of therapy to death was 9 months. There were no differences between the three treatment programs as regards survival. In adults the remission rate was 15 per cent for combination therapy, 21 per cent for 6-mercaptopurine and 7 per cent for Methotrexate. As regards survival in adults, early deaths were more common in patients who received MTX as initial therapy, whereas after 5 months survival was somewhat better in those patients receiving combination therapy. In both children and adults there was no evidence that prior treatment with one of the antimetabolites altered response to the other antimetabolite. This result differs from those in animal models, and its effect on our concept of the mechanism of resistance is discussed. Responsiveness to the second course of antimetabolite therapy (Phase II) was as good as that to the first course of treatment. This was true for the remission rate, remission duration, and even for survival when appropriate corrections were made. Thus, responsiveness to drug therapy is maintained as the disease progresses temporally. It may be concluded therefore that new agents can be effectively studied in patients with "late" disease. Responsiveness to Phase II therapy was independent of responsiveness to Phase I. The most common and severe toxic manifestations related to the bone marrow and gastrointestinal tract. There were no major differences quantitatively in the toxicity for the three treatment programs in children in spite of the fact that the drugs were given in full dosage in the combination program. Oral ulcers and a generalized erythematous rash occurred significantly more frequently in patients receiving Methotrexate. Jaundice was significantly more frequent in adults and in patients receiving 6-MP.

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To evaluate whether In-111 capromab pendetide (an antibody conjugate directed to a glycoprotein found primarily on the cell membrane of prostate tissue) radioimmunoscintigraphy can localize residual or metastatic prostatic carcinoma in 15 patients after prostatectomy and lymphadenectomy for prostatic carcinoma with rising serum prostate-specific antigen. One patient with 0.6 ng/ml serum prostate-specific antigen had normal imaging results and 14 patients had scintigraphic evidence of residual prostatic bed or metastatic prostatic carcinoma. Two patients with borderline abnormal bone scans had abnormal activity in the same regions on In-111 capromab pendetide images. All patients had negative radiographic abdominal and pelvic cross-sectional prestudy images, and there were no adverse effects related to In-111 capromab pendetide infusion and little human antimouse antibody response.

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Abstract-We are investigating interventional MRI (iMRI) guided radiofrequency thermal ablation for the minimally invasive treatment of the prostate cancer. Nuclear medicine can detect and localize tumor in the prostate not reliably seen in MRI. We intend to combine the advantages of functional images such as nuclear medicine SPECT with iMRI-guided treatments. Our concept is to first register the low-resolution SPECT with a high-resolution MRI volume. Then by registering the high-resolution MR image with live-time iMRI acquisitions, we can, in turn, map the functional data and high-resolution anatomic information to live-time iMRI images for improved tumor targeting. For the first step, we used a three-dimensional mutual information registration method. For the latter, we developed a robust slice to volume (SV) registration algorithm with special features. The concept was tested using image data from three patients and three volunteers. The SV registration accuracy was 0 4 mm 0 2 mm as compared to our volume-to-volume registration that was previously shown to be quite accurate for these image pairs. With our image registration and fusion software, simulation experiments show that it is quite feasible to incorporate SPECT and high-resolution MRI into the iMRI-guided minimally invasive treatment procedures.Index Terms-Fusion visualization, image-guided minimally invasive therapy, image registration, interventional MRI, prostate cancer, SPECT.

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