Hence, there has been a search for non-invasive procedures for PCP diagnosis, including a variety of Nuclear Medicine scans:
Gallium-67 citrate scanning of the chest is more sensitive means of detecting PCP than plain chest radiographs. Scans are usually performed 72 hours after the i.v. injection of 5 mCi of Gallium-67 citrate. Scans at 24 and 48 hours may be performed when a more immediate result is required; however, soft tissue background and blood pool activity can be normal on 24 hour images.
In-111 labeled white blood cells may be used for the detection of pulmonary infections or inflammatory conditions in AIDS. Ga-67 citrate, however, is more sensitive (100%%) for diffuse processes showing greater uptake than In-111 WBC's (sensitivity 40%%) in patients with PCP (2). In-111 white blood cells are more sensitive for focal pulmonary processes, particularly bacterial pneumonias which are also usually evident on radiographic examination.
Clearance of Tc-99m DTPA radioaerosol from the lungs has also been used in the diagnosis of PCP. It is generally believed that alveolar damage in PCP results in increased alveolar-capillary membrane permeability which causes increased radioaerosol clearance (Rosso). Picard found aerosol clearance to be more sensitive than Ga-67 scans of grade 3 or 4 for PCP while Rosso reported that an aerosol clearance of >4.5%% per min. was both sensitive (85%%) and specific (87%%) for the diagnosis of PCP (3), and that DTPA was useful for detecting lung disease when chest X-ray and/or PaO2 are normal.
Non-specific uptake of polyclonal IgG labeled with In-111 in infection has been studied in humans and rats and led Goldenberg et al to develop a monoclonal antibody directed against the P.carinii organism. They report a sensitivity of 85.7%% and specificity of 86.7%% for PCP using a Tc-99m labeled Fab fragment of a murine monoclonal antibody to PCP (4).
In general, radioscintigraphic techniques are sensitive for the detection of PCP, especially Ga-67 scans. However, the specificity for PCP is lacking. Several authors have recently reported studies describing patterns of Ga-67 uptake that have improved specificity for PCP. In a study of 86 Ga-67 citrate chest scans on 71 patients with AIDS presenting with fever and/or respiratory symptoms, and a study of 180 HIV+ patients with suspected pulmonary infections, Kramer et al report that Ga scanning has a high sensitivity for PCP detection of 98%%, similar to the findings of Barron et al who reported a sensitivity of >90%% (5-8). The overall specificity for a positive scan was considerably lower - 51%% in Kramer's study and 74%% recorded by Barron. More selective criteria for evaluating Ga scans in the setting of AIDS was found to increase the specificity. A positive Ga scan associated with a normal CXR had a specificity of 77%% in Kramer's study and 85%% for Barron. Kramer et al described 5 patterns of Ga uptake into the lungs:
They report that the specificity for PCP is increased in patients with scans showing diffuse uptake of Ga particularly when the pattern is heterogeneous. When only a diffuse pattern of Ga uptake was considered, Kramer found the specificity for PCP to increase to 83%% with a positive predictive value (PPV) of 72%% compared to a PPV of 62%% for any type of intrapulmonary uptake. Barron found a diffuse pattern specificity of 85%%. The heterogeneous pattern of uptake was described as uptake involving >50%% of total lung area with localized areas of greater concentration and areas of relative sparing. The PPV for heterogeneous uptake was 87%%. The PPV for homogeneous patterns (qualitatively uniform uptake throughout the lung) was just 64%% In addition, they found an increased specificity for PCP in those scans with uptake intensity of Ga graded 2+ and higher (see following). The PPV for PCP of a scan increased from 79%% for all scans grade 2 or higher, to 95%% if only grade 4 scans were considered. Similarly the PPV increased from 64%% to 77%% from grade 2 uptake to grade 4.
The cause of heterogeneous uptake in PCP was unclear and did not seem to be related to concomitant underlying lung disease, smoking, or the severity of the disease. It is possible that as AIDS patients are now living long enough to experience repeated episodes of infection, previously affected regions of the lung which have incurred damage may be less hospitable to new PCP infection. Several authors have found that the chest X-ray is more likely to show densities confined to or predominantly in the upper lobes and cyst formation is more common in patients treated with prophylactic pentamidine. In these cases the chest X-ray abnormalities are restricted to the areas of the lung not reached by the aerosol.
In a case recently reported by Katial et al (9), bibasilar uptake of Ga into the lungs is described in an AIDS patient with fever. Localization of the Ga uptake was useful in directing the bronchoscopy for bronchoalveolar lavage and transbronchial biopsy leading to a diagnosis of PCP. After complete resolution of the illness, an aerosol ventilation study demonstrated prominent ventilation defects in the lung bases corresponding with the previous Ga uptake with no residual Ga uptake. This lead to the speculation that the focal occurrence of PCP in the basilar segments was due to reduced delivery of aerosolized pentamidine to these areas.
In those cases with very intense heterogeneous uptake of Ga throughout much of the lungs and a negative chest X-ray, one should have a high suspicion for PCP. In these cases, specific diagnosis should be pursued because prompt institution of appropriate therapy for PCP is believed to improve outcome. The location of Ga uptake on the scan can direct bronchoalveolar lavage and transbronchial biopsy.
2. Fineman DS, Palestro C, Kim CK et al Radiology 1989;170:677-680.
3. Rosso J, Guillon JM, Parrot M et al Tc-99m-DTPA aerosol and gallium-67 scanning in pulmonary complications of human immunodeficiency virus infection J Nucl Med 1992;331(1):81-87.
4. Goldenberg DM, Sharkey RM, Udem S et al Immunoscintigraphy of P.carinii pneumonia in AIDS patients J Nucl Med 1994;35(6):1028-1034.
5. Kramer EL, Sanger JS, Garay SM et al. Gallium-67 scans of the chest in patients with AIDS. J Nucl Med 1987;28(7):1107-1114.
6. Kramer EL, Sanger JS, Garay SM et al. Diagnostic Implications of gallium-67 chest-scan patterns in HIV+ patients. Radiology 1989;170:671-676.
7. Kramer EL, Sanger JS. Nuclear Medicine in the management of the AIDS patient. Nuclear Medicine Annual 1990.
8. Kramer EL. PCP, AIDS and Nuclear Medicine. Editorial. J Nucl Med 1994;35:1034-1037.
9. Katial R, Honeycutt W, Oswald SG. PCP presenting as focal bibasilar uptake on gallium scan during aerosolized pentamidine prophylaxis. J Nucl Med 1994;35:1038-1040.
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