(99m)Tc glucarate as a potential radiopharmaceutical agent for assessment of tumor viability: from bench to the bed side

Abstract

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. (99m)Tc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with (18)F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent (99m)Tc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent (99m)Tc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. (99m)Tc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy.

Keywords: 99mTc glucarate; SPECT imaging; Tumor viability.

Figure 1

A 65-year-old male, a case of small cell lung carcinoma. Planar and SPECT ^99mTc-glucarate study shows avid tracer concentration in the right upper lobe lung lesion, better seen in the SPECT study

Figure 2

A 60-year-old male, a case of NSCLC. There is avid ^99mTc-glucarate concentration in the mass lesion in the left lung corresponding to the primary lesion seen on the CT scan. The metastatic lesion in contralateral lung, seen better in the lung window in the CT scan, also shows avid glucarate concentration

Figure 3

A 50-year-old male with SCC involving right lung upper lobe with extension into the chest wall. ^99mTc-glucarate SPECT scintigraphy shows avid tracer concentration in the primary lesion

Figure 4

A 79-year-old male with a squamous cell carcinoma in the left lung upper lobe. There is avid concentration of ^99mTc-glucarate in the primary lesion in the pre-treatment/baseline study. (a) Significant regression in the size of the mass lesion with corresponding decreased radiotracer uptake is noted post 3 cycles of chemotherapy. (b) Further decrease in radiotracer uptake is seen post 6 cycles of chemotherapy,(c) with evidence of stable disease in corresponding CT scan

Figure 5

A 51-year-old male, a case of SCLC. Pre and post 3 cycles of chemotherapy. Scan shows good response to treatment

Figure 6

A 78-year-old male, a case of NSCLC. Baseline scan (a) shows avid tracer concentration in the primary lesion in right lung. Post 3 cycles of chemotherapy, the lesion shows complete functional response with residual lung changes in CT. (b) On followup, a recurrent lesion (c) is seen after 8 months

Figure 7

A 53-year-old male, a case of NSCLC. There is avid ^99mTc-glucarate concentration in the mass in right lung, rib, and axillary nodal metastasis in the baseline/pre-treatment study (D). There is a significant regression in the size of the primary lesion in lung and axillary nodal metastasis post 3 cycles of chemotherapy (E), with corresponding clinical/symptomatic improvement

Figure 8

A 57-year-old old male, a case of carcinoma of the base of tongue. Avid ^99mTc-glucarate concentration is seen in the tumor corresponding to the lesion in MRI in the baseline study

Figure 9

A 53-year-old male, a case of carcinoma of pyriform fossa and base of tongue. Avid ^99mTc-glucarate concentration is seen in the tumor, corresponding to the lesion in CT scan, in the baseline study

Figure 10

A 31-year-old male, a case of NSCLC. Both 18-F FDG PET-CT and ^99mTc-glucarate study show tracer concentration in the primary lesion and bone metastasis