Nuclear Medicine in the Assessment of Adverse Effects of Cancer Therapy in the Lung, Kidney, Gastrointestinal Tract, and Central Nervous System

Abstract

Radiotherapy or chemotherapy and new drugs and strategies in oncology can produce damage in normal organs and tissues affecting the quality of life of the patient. Pulmonary toxicity is frequently seen in patients treated with bleomycin or other chemotherapeutic agents.

The most common clinical form of bleomycin pulmonary toxicity is the subacute condition, which may progress to lung fibrosis and death, if not recognized and appropriately managed. The diagnosis is usually established by a combination of clinical, radiographic, and pulmonary function test abnormalities. X-ray and high-resolution CT scan findings are used to identify pulmonary fibrosis. ⁶⁷Ga-citrate scintigraphy has been used to detect and assess the extent of pulmonary toxicity related to bleomycin in patients who otherwise have normal chest radiographs.

Since conventional CT scanning is not able to distinguish fibrosis from active inflammation, [¹⁸F]FDG-PET/CT has been suggested as a tool to indicate the resolution of disease activity. Moreover, [18F]FDG-PET/CT could be useful to detect early preclinical pneumonitis induced by bleomycin. Similarly, as pulmonary permeability can be altered by chemotherapy, ^99mTc-DTPA aerosols can be used to assess a potential reduction of epithelial permeability.

Acute radiation lung injury can occur within 1–3 months after radiation therapy of the thorax, whereas lung fibrosis can develop 6–24 months later, leading to progressive impairment of pulmonary function. Clinical manifestations, chest radiographs, and pulmonary function tests may help to establish an early diagnosis. ⁶⁷Ga-citrate scintigraphic abnormalities can be demonstrated in the acute phase often before radiologic changes become apparent. Moreover, ¹¹¹In-pentetreotide may have a role in the differential diagnosis of patients with complaints after radiotherapy and for monitoring response to corticosteroid therapy. [¹⁸F]FDG uptake in the irradiated region can be observed up to about 2 months following therapy. The persistence of activity beyond 8 weeks raises the likelihood of persistence of disease within the irradiated region. Lung scintigraphy with ^99mTc-DTPA aerosol and ^99mTc-MAA (macroaggregates of albumin) has been performed to assess radiation-induced ventilation/perfusion changes.

Drugs for the treatment of abdominal malignancies, such as cisplatin and ifosfamide, and abdominal radiation can cause renal damage. Chemotherapy-induced nephropathy can be identified with quantitative measurement of glomerular filtration rate. ^99mTc-DTPA has become the preferred radiopharmaceutical because of wide availability and low cost. ^99mTc-DMSA scintigraphy can be used to establish tubular dysfunction induced by nephrotoxic drugs. Nuclear medicine techniques also offer the possibility to follow the clinical evolution of radiation nephropathy. In this scenario, ^99mTc-MDP bone scintigraphy can show increased kidney uptake early after radiation when the treatment field has included the kidneys. Over the subsequent 6–12 months, the uptake decreases to normal or below normal levels, associated with the loss of function. Renography with ^99mTc-DTPA can be performed to assess radiation nephropathy. The ^99mTc-DTPA captopril renography test has been used to investigate the relation between small-vessel injury due to radiation and hypertension.

Nuclear medicine examinations can play a role in the detection of radiation-induced digestive tract damage. In cancers of the cervix, endometrium, ovary, prostate, bladder, or rectum, radiation therapy is often required. Radiation proctitis is usually self-limited and resolves within a month after the conclusion of therapy. Damage of the small bowel is seen in 0.5–15% of the patients. Chronic injuries to the small bowel are manifest 6 and 24 months after radiation. Ileal dysfunction is due to bile acid malabsorption, to bacterial overgrowth in the small bowel, or to the combination of both. ⁷⁵Se-homocholic acid conjugated with taurine (⁷⁵Se-HCAT) and the [¹⁴C]glycocholic breath test can be used to differentiate between normal functioning ileum (both tests negative) and ileal dysfunction (one or both tests positive). The combination of both tests may allow the differentiation between bile acid malabsorption (⁷⁵Se-HCAT positive) and bacterial overgrowth (⁷⁵Se-HCAT negative).

Radionuclide-based techniques may also help to document the benefit of innovative therapeutic approaches such as the use of somatostatin analogs (SOM230). In cases of radiotherapy- and chemotherapy-associated liver injury, radionuclide studies can be performed using ^99mTc-iminodiacetic acid or ^99mTc-colloid. In patients receiving radiotherapy, the most common finding is the loss of function of the part of the liver involved in the radiation field, with a reduced uptake in irradiated areas. Recently, acute radiation-induced hepatitis has been reported as a potential cause of false-positive findings of malignancy on [¹⁸F]FDG-PET scans. Moreover, radiotherapy esophagitis can be observed on [¹⁸F]FDG-PET scans.

Leucocytes labeled with ¹¹¹In-oxine or with ^99mTc-HMPAO or [¹⁸F]FDG can be used in patients with suspected radiation enterocolitis.

Inhibitors of the T-cell-mediated immune response, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-1 L), also known as immunotherapy, can produce potentially fatal adverse effects due to the T-cell activation and proliferation leading to potentially autoreactive T-cells and inflammatory adverse effects across a range of tissues, contributing to immune-mediated side effects. Most of serious adverse effects with CTLA-4 inhibitors are associated with gastrointestinal tract disturbances and respiratory and urination problems. Programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-1 L) serious adverse effects include colitis, hepatitis, pneumonitis, and renal failure. An improved identification of this toxicity may allow for improved treatment tailoring and clinical outcome.