Nuclear Medicine in HIV Update with FDG PET
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1 Nuclear Medicine in HIV Update with FDG PET Mike Sathekge, MB ChB, M Med (Nucl Med), PhD HOD: University of Pretoria Introduction Outline Brief about general nuclear medicine FDG in HIV: Update & Potential 1
2 HIV/AIDS: EPIDEMIOLOGY Sub-Saharan Africa < 10% of the world s population, yet contains; 90% of the paediatric cases 68% of the adult cases 76% of the global AIDS-related deaths HIV/AIDS: South Africa 5.5 million of the 33.2 million > 1,400 new infections p/d, (~ to nearly one infection every minute) Average of 950 AIDS deaths (~to one AIDS death every 90 seconds) Projections by 2015 Cumulative AIDS deaths 5.4 million Orphaned children; 2.5 million 2
3 Three Different Possible Outcomes of HIV infection to a cell Productive Infection Occurs when activated T cell is infected, resulting in production of progeny virions Latent Infection After viral production shuts down at end of production phase Abortive Infection When resting T cells (comprise > 98%) is infected Three possible ways by which CD4 T cells could disappear from the blood: The immune system stops making new CD4 cells CD4 cells die in the blood CD4 cells leave the blood 3
4 CD4 + (cells/µl) Opportunistic diseases in the course of HIV-infection Seroconversion: Acute retroviral syndrome Pneumococcal pneumonia Candida vaginitis ITP TB Oral Candida-infection Kaposi sarcoma Lymphoma Dementia Oral haircell-leukoplacia Cachexia Toxoplasmosis PCP HSV Candida esophagitis Cryptococcosis MAC CMV Years after infection TB and HIV Infection 11 million (TB and HIV co-infected) TB infection HIV infection 2 Billion 33 Million 4
5 Adverse Drug Effects Mitochondrial dysfunction Metabolic abnormalities Hematologic complications Allergic reactions Lactic acidosis Hepatic toxicity Pancreatitis Peripheral neuropathy Lipodystrophy Fat accumulation Lipoatrophy Hyperlipidemia/? Premature CAD Bone marrow suppression Hypersensitivity reactions Skin rashes Hyperglycemia Insulin resistance/dm Bone disorders: oesteoporosis and osteopenia HAART INCREASES INCIDENCE OF NADC!! HIV-Associated Lipodystrophy Hyperlipidemia Insulin resistance Fat accumulation Fat atrophy 5
6 Clinical and immunopathological course of HIV associated TB Neurological Manifestations 6
7 TUBERCULOMA Clinical request for Toxoplasmosis vs Lymphoma AIDS DEMENTIA S l i d e - 5 7
8 CXR, Tl, Ga CXR Negative Ga67- Negative Tl201 Positive Kaposi Sarcoma Abdel-Dayem 2004 GALLIUM IN AIDS - PCP Severe PCP Mild PCP Post Treatment Abdel-Dayem
9 SEQUENTIAL THALLIUM AND GALLIUM SCANS IN AIDS PATIENTS Ga Thallium Kaposi Negative Positive Lymphoma Positive Positive Opportunistic Infections Positive Negative Cryptosporoidosis Ga 4 hrs Ga 24 hrs 9
10 CMV Host Immunocompetent Immunocompromised Presentation Heterophile negative mononucleosis syndrome Retinitis Hepatitis Pneumonitis Gastritis Esophagitis Polyradiculopathy Myelitis HIV: Opportunistic Disease CMV 10
11 TB and HIV Infection 11 million (TB and HIV co-infected) TB infection HIV infection 2 Billion 33 Million TB: THYROID 11
12 SPECT-CT: PULMONARY TB SPECT-CT: TB BREAST 12
13 Ga-67 IN HIV & Extrapulmonary TB TB: HIP JOINT 13
14 Review HIV & FDG PET FDG in the CNS may identify ADC Lymphoma vs Toxo Nodal uptake patterns Head & Neck: acute disease Generalized: mid stage disease Abdominal: late stage disease FDG may be useful for Staging disease Monitoring response to therapy FDG-PET & AIDS O Doherty et al. (J NM 1997; 38:1575) 57 AIDS patients had body imaging 92% sensitivity & 94% specificity for localization of focal pathology needing Rx. Intensity of uptake not useful for distinguishing benign from malignant processes 14
15 FDG-PET & AIDS Lymphoma Toxoplasmosis Pierce et al. (Ann Int Med 1995; 123: ) Hoffman et al. (J Nucl Med 1993; 34: ) FDG uptake: Lipodystrophy RESULTS FDG uptake: Lipodystrophy vs Non-lipodystrophy 39 patients Duration of Rx Me/ra SUV sc (sd) SUV mus (sd) Therapy Naive (0.14) 0.59(0.15) No Lipodystrophy 5M( m) 0.46(0.24) 0.62(0.17) Lipodystrophy 12M(6-24M) 0.9(0.15) 0.63(0.18) Sathekge et al., Nucl Med Commun
16 HAART with lipodystrophy: FDG uptake in subcutaneous fat 1a 1b FDG Uptake reflect ongoing apoptosis SUVmean SUV correlate with Rx duration & inversely correlate with viral load HAART Naive 0.3 No Lipodystrophy SUV Viral Load Lipodystrophy Viral Load copy number/ml Treatment Duration in Months
17 Conclusion FDG uptake by subcutaneous HIV patients under HAART presenting with lipodystrophy therapy naïve HIV patients patients under HAART that did not suffer from lipodystrophy. Contrary to available preclinical data, HAART did not influence FDG uptake by human skeletal muscle tissue under basal sedentary conditions FDG Relation to CD4 & L/N Results Predominant sites of lymph node: cervical and axillary region, followed by the inguinal Averaged SUVmean values: 3.4 (range: ). Median CD4 cell count : 187/mL (range: ml). Median viral load 835 copies/ml (range: <50(0) ml). 17
18 Results Sathekge et al., Nucl Med Commun a 1b 18
19 Potential Apoptotic Hypothesis Results LN (n=18) Lung (n=5) Pleural (n=6) Bone (n=4) Joints (n=3) Early 6.3(1.6) 8.2(5.8) 1.3(0.4) 7.2 (1.3) 4.7(0.5) Delayed 7.9(2.4) 11.1(7.2) 1.7(0.6) 10.7 (3.6) 5.2(1.4) Ret Index 25(17.8) 35(9.0) 21(24) 45(25.5) 23(22) 19
20 HIV & TB: Extrapulmonary TB Results PET vs CT PET demonstrated 50% more lymph nodes than CT PET & CT were equal for lung(diff.act. 2/5 pts)/osseous/joints PET was inferior to CT for pleural involvement PET did not alter the therapy planning Sathekge et al., Nuklearmedizin 2010 TB lymphadenitis 20
21 TB Spine HIV: FOU 21
22 HIV: TB Pericarditis FDG PET FOR ONCOLOGY IN HIV & TB ENDEMIC AREA Drawback in oncology diagnosis/staging Zhuang H et al JNM 2001 Dual-Phase FDG PET 22
23 Dual-phase imaging & SUV max not helpful in TB SUV1max > 2.5: sens =85.7 %, spec =25%. Ret index>10%: sens =85.7 %, spec =50%. Sathekge et al: SAMJ Staging (L/N) in HIV & TB Results HIV+/TB-/CA- HIV+/TB+/CA- HIV-/TB+/CA- HIV-/TB-/CA+ Sathekge et al., Q J Nucl Med 23
24 Results Figure 2. Sathekge et al., Q J Nucl Med HIV & TB L/N 24
25 Conclusion Patients presenting with both HIV and TB (HIV+/TB+/CA-) present with significantly more sites of LN involvement and LNs involved are also metabolically more active when compared to HIV+/TB-/CA- and HIV-/TB+/CA patients. A significant difference in FDG uptake by LNs could be only documented between HIV+/TB-/CApatients and HIV-/TB-/CA+ patients. FDG PET is not reliable for assessing malignant lymph node involvement in HIV+, TB+ or HIV+/TB+ patients with VL is not 0. TB: MONITORING THERAPY RESPONSE BEFORE THERAPY 25
26 TB: MONITORING THERAPY RESPONSE 3 MONTHS AFTER THERAPY HIV: NHL Follow-up Immuno-virological status 26
27 What about IRIS SAPIT in South Africa with interim data on mortality rates indicating a 55% reduction of mortality in the integrated TB-HIV arm Integrated TB-HIV arm: IRIS or Failure to Respond? 27
28 Importance of FDG PET in HIV & TB Improve treatment strategy in both HIV & TB New Probes Indicated Improve TB diagnosis in HIV-infected patients, extrapulmonary TB Pathophysiology of IRIS to improve its DX/prognosis & Rx (without information incoherent conclusion) 28
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