Renal Function Assessment During Peptide Receptor Radionuclide Therapy.

Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51-ethylenediaminetetraacetic acid (EDTA), or measurement of Tc-99m-MAG3 clearance, particularly in patients with preexisting risk factors for long-term nephrotoxicity. Proximal tubular reabsorption and interstitial retention of tracers result in excessive renal irradiation. Coinfusion of positively charged amino acids, such as l-lysine and l-arginine, is recommended to decrease the renal retention of the tracers by inhibiting the proximal tubular reabsorption. Furthermore, nephrotoxicity may be reduced by dose fractionation. Patient-specific dosimetric studies showed that renal biological effective dose of <0Gy was safe for patients without any risk factors. A renal threshold value <28Gy was recommended for patients with risk factors. Despite kidney protection, renal function impairment can occur after PRRT, especially in patients with risk factors and high single or cumulative renal absorbed dose. Therefore, patient-specific dosimetry may be helpful in minimizing the renal absorbed dose while maximizing the tumor dose. In addition, close and accurate renal function monitoring using more precise methods, rather than plasma creatinine levels, is essential to diagnose the early renal functional changes and to follow-up the renal function during the treatment.

Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment.

PURPOSE: Sialadenitis is a well-recognized adverse effect of high-dose radioactive iodine treatment. This study was undertaken to determine whether Tc-99m pertechnetate salivary gland scintigraphy may be used for objective assessment of salivary gland function in patients with thyroid cancer treated with I-131. PATIENTS AND METHODS: The study group consisted of 71 patients (16 men, 55 women) with a mean age of 44 years (range, 16 to 73 years). Twenty-six (37%) patients were not given any radioiodine, and 18, 16, and 11 patients received doses of 100, 150, or 200 mCi (or higher), respectively. Parotid and submandibular glands were evaluated based on a four-grade scoring system. Correlation between the type of surgery, administered dose, time since therapy, subjective symptoms, and findings of salivary gland scintigraphy were evaluated. RESULTS: Subjective symptoms were questioned in 39 of the 45 patients who received radioactive iodine treatment. Fifty-four percent (21 of 39) of the patients reported xerostomia, of whom 86% (18 of 21) showed salivary gland dysfunction. Objective salivary gland dysfunction was observed in 69% (31 of 45) of patients. In 81% of the patients, the parotid glands were affected; in 13% of the patients, the submandibular glands were affected; and in 6%, both were affected ( < 0.000001). The frequency of salivary gland dysfunction showed a dose dependence to cumulative activity ( = 0.007). A greater complication rate was observed in patients with total thyroidectomy compared with subtotal surgery, although the correlation was not significant ( = 0.625). CONCLUSIONS: Parenchymal damage to the salivary glands induced by radioactive iodine treatment can be evaluated by salivary gland scintigraphy. The impairment is worse in the parotid glands and increases with the total dose.