Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer.

BACKGROUND: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. RESULTS: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first-line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. CONCLUSION: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer.

Spontaneous remission of peripelvic renal cysts.

Three cases are presented of spontaneous regression of peripelvic renal cysts. The lesions were manifested by lateral extrinsic pressure defects in the renal pelvis and major calices (all 3 cases), and selective renal angiography showing stretching of vessels plus sharply defined defects in the nephrographic phase (2 patients). In 1 case the mass disappeared following trauma to the flank, while in the remaining 2 cases it disappeared spontaneously.

The catheter. How to use and when not to use.

Catheterization should not be used without true indication. Careful control of hydration, sedation, anesthesia and use of anticholinergic agents before, during and after operation can do a great deal to prevent the need for catheterization. When the procedure is necessary, simple, inexpensive measures of care usually are sufficient. Prophylactic antisepsis before and after, with reexamination of the urine after discontinuance of antiseptic drugs to make sure there is no recrudescence, prevents acute and chronic infections. The catheter recommended for routine male and female catheterization is the 14-16 (French) olive tip coude (Tieman) catheter or the Tieman-Foley. Closed drainage systems are the best. Continuous irrigation is without value. Water is an excellent irrigant. Calcium deposits are prevented by Renacidin(R) instillation and acetic acid irrigation.